The interaction of chemokines and their cognate receptors (CCRs) forms a key signaling network de... more The interaction of chemokines and their cognate receptors (CCRs) forms a key signaling network dedicated to promoting an inflammatory tumor microenvironment (TME), leukocyte recruitment and activation, angiogenesis, and growth in all stages of various cancers. Aberrant expressions of chemokines and CCRs are found to correlate with immunosuppression, metastasis, drug resistance, and poor prognosis in breast cancer patients. Several specific inhibitors for chemokines or CCRs are currently tested in clinical trials of multiple cancers. To date, no pan-CCR inhibitor has been developed as a cancer therapy, which is expected to have more clinical advantages than the agent with specificity for a single CCR. We collaborated with Dr. Filip Fratev's team (Micar21, Bulgaria) to develop potent pan-CCR inhibitors for breast cancer. By performing a virtual screen of 4 million compounds based on the analyses of Pharmacophore-based Docking, Induced-fit Docking, Molecular Dynamics, and Metadynam...
In the present study, fifteen benzimidazolyl-2-hydrazones 7a-7o of fluoro-, hydroxy- and methoxy-... more In the present study, fifteen benzimidazolyl-2-hydrazones 7a-7o of fluoro-, hydroxy- and methoxy-substituted benzaldehydes and 1,3-benzodioxole-5-carbaldehyde were synthesized and their structure was identified by IR, NMR, and elemental analysis. The compounds 7j 2-(3-hydroxybenzylidene)-1-(5(6)-methyl-1H-benzimidazol-2-yl)hydrazone and 7i 2-(3-hydroxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazone have exerted the strongest anthelmintic activity (100 % after 24 h incubation period at 37°C) against isolated muscle larvae of Trichinella spiralis in an in vitro experiment. The in vitro cytotoxicity assay towards MCF-7 breast cancer cells and mouse embryo fibroblasts 3T3 showed that the studied benzimidazolyl-2-hydrazones exhibit low to moderate cytotoxic effects. The ability of the studied benzimidazolyl-2-hydrazones to modulate microtubule polymerization was confirmed and suggested that their anthelmintic action is mediated through inhibition of the tubulin polymerization likewise the other known benzimidazole anthelmitics. It was also shown that the four most promising benzimidazolyl-2-hydrazones do not affect significantly the AChE activity even at high tested concentration, thus indicating that they do not have the potential for neurotoxic effects. The binding mode of compounds 7j and 7n in the colchicine-binding site of tubulin were clarified by molecular docking simulations. Taken together, these results demonstrate that for the synthesized benzimidazole derivatives the anthelmintic activity against T. spiralis and the inhibition of tubulin polymerization are closely related.
The mutations in the spike protein of SARS-CoV-2 Omicron variant (B.1.1.529 lineage) gave rise to... more The mutations in the spike protein of SARS-CoV-2 Omicron variant (B.1.1.529 lineage) gave rise to questions, but the data on the mechanism of action at the molecular level is limited. In this study, we present the Free energy of perturbation (FEP) data about the RBD-hACE2 binding of this new variant.We identified two groups of mutations located close to the most contributing substitutions Q498R and Q493R, which altered significantly the RBD-hACE2 interactions. The Q498R, Y505H and G496S mutations, in addition to N501Y, highly increased the binding to hACE2. They enhanced the binding by 98, 14 and 13 folds, respectively, which transforms the S1-RBD to a picomolar binder. However, in contrast to the case in mice the Q493R/K mutations, in a combination with K417N and T478K, dramatically reduced the S1 RBD binding by over 100 folds. The N440K, G446S and T478K substitutions had lesser contribution. Thus, the total effect of these nine mutations located on the interaction surface of RBD-h...
The N501Y and K417N mutations in the spike protein of SARS-CoV-2 and their combination gave rise ... more The N501Y and K417N mutations in the spike protein of SARS-CoV-2 and their combination gave rise to questions, but the data on their mechanism of action at the molecular level were limited. In this study, we present free energy perturbation (FEP) calculations, performed at the end of December 2020, for the interactions of the spike S1 receptor-binding domain (RBD) with both the ACE2 receptor and an antibody derived from COVID-19 patients. Our results showed that the S1 RBD-ACE2 interactions were significantly increased whereas those with the STE90-C11 antibody dramatically decreased. The K417N mutation in a combination with N501Y fully abolished the antibody effect. However, Lys417Asn seems to have a compensatory mechanism of action increasing the S1 RBD-ACE2 free energy of binding. This may explain the increased spread of the virus observed in the U.K. and South Africa and also gives rise to an important question regarding the possible human immune response and the success of the already available vaccines. Notably, when the experimental data became available confirming our calculations, it was demonstrated that protein-protein FEP can be a useful tool for providing urgent data to the scientific community.
The Mu variant of SARS-CoV-2 has been recently classified as a variant of interest (VOI) by the w... more The Mu variant of SARS-CoV-2 has been recently classified as a variant of interest (VOI) by the world health organization (WHO) but limited data are available at the moment. In particular, a special attention was given to the R346K mutation located in the receptor binding domain (RBD). In the current study we performed Free energy of perturbation (FEP) calculations to elucidate it possible impact on a set of neutralizing monoclonal antibodies (mAbs) which have been shown to be strong inhibitors of the most other known COVID-19 variants. Our results show that R346K affects the class 2 antibodies but its effect is not so significant (0.66 kcal/mol); i.e. reduces the binding with RBD about 3 times. An identical value was calculated also in the presence of both class 1 and class 2 antibodies (BD-812/836). Further, a similar reduction in the binding (0.4 kcal/mol) was obtained for BD-821/771 pair of mAbs. For comparison, the addition of K417N mutation, present in the newly registered Mu ...
Benzimidazole anthelmintic drugs hold promise for repurposing as cancer treatments due to their i... more Benzimidazole anthelmintic drugs hold promise for repurposing as cancer treatments due to their interference with tubulin polymerization and depolymerization, manifesting anticancer properties. We explored the potential of benzimidazole compounds with a piperazine fragment at C-2 as tubulin-targeting agents. In particular, we assessed their anthelmintic activity against isolated Trichinella spiralis muscle larvae and their effects on glioblastoma (U-87 MG) and breast cancer (MDA-MB-231) cell lines. Compound 7c demonstrated exceptional anthelmintic efficacy, achieving a 92.7% reduction in parasite activity at 100 μg/mL after 48 hours. In vitro cytotoxicity analysis of MDA-MB 231 and U87 MG cell lines showed that derivatives 7b, 7d, and 7c displayed lower IC50 values compared to albendazole (ABZ), the control. These piperazine benzimidazoles effectively reduced cell migration in both cell lines, with compound 7c exhibiting the most significant reduction, making it a promising candidat...
The N501Y and K417N mutations in spike protein of SARS-CoV-2 and their combination arise question... more The N501Y and K417N mutations in spike protein of SARS-CoV-2 and their combination arise questions but the data about their mechanism of action at molecular level is limited. Here, we present Free energy perturbation (FEP) calculations for the interactions of the spike S1 receptor binding domain (RBD) with both the ACE2 receptor and an antibody derived from COVID-19 patients. Our results shown that the S1 RBD-ACE2 interactions were significantly increased whereas those with the STE90-C11 antibody dramatically decreased; about over 100 times. The K417N mutation had much more pronounced effect and in a combination with N501Y fully abolished the antibody effect. This may explain the observed in UK and South Africa more spread of the virus but also raise an important question about the possible human immune response and the success of already available vaccines.
In recent years, the mammalian GlyT2 transporter have emerged as a promising target for the devel... more In recent years, the mammalian GlyT2 transporter have emerged as a promising target for the development of anti-chronic pain agents. In our current work, we discovered a new set of promising hits that inhibit the glycine transport at nano and micromolar activity and have excellent selectivity over GlyT1 (as shown by in vitro studies), using a newly designed virtual screening (VS) protocol that combines a structure-based pharmacophore and docking screens. Furthermore, the free energy perturbation (FEP+ protocol) calculations and molecular dynamics (MD) studies revealed the GlyT2 amino acid residues critical for the binding and selectivity of both Glycine and our Lead1 compound. The FEP+ results well-matched available literature mutational data proving the quality of generated GlyT2 structure. Based on these calculations we propose that Lead1 may also be a strong inhibitor of the neutral and basic amino acid transporter B (0+) (SLC6A14). Thus, the subsequent lead optimization and char...
Recent improvements to the free energy perturbation (FEP) calculations, especially FEP+ , establi... more Recent improvements to the free energy perturbation (FEP) calculations, especially FEP+ , established their utility for pharmaceutical lead optimization. Herein, we propose a modified version of the FEP/REST (i.e., replica exchange with solute tempering) sampling protocol, based on detail studies on several targets by probing a large number of perturbations with different sampling schemes. Improved FEP+ binding affinity predictions for regular flexible-loop motions and considerable structural changes can be obtained by extending the prior to REST (pre-REST) sampling time from 0.24 ns/λ to 5 ns/λ and 2 × 10 ns/λ, respectively. With this new protocol, much more precise ∆∆G values of the individual perturbations, including the sign of the transformations and decreased error were obtained. We extended the REST simulations from 5 ns to 8 ns to achieve reasonable free energy convergence. Implementing REST to the entire ligand as opposed to solely the perturbed region, and also some import...
Estimating the correct binding modes of ligands in protein-ligand complexes is not only crucial i... more Estimating the correct binding modes of ligands in protein-ligand complexes is not only crucial in the drug discovery process, but also for elucidating potential toxicity mechanisms. In the current paper, we discuss and demonstrate a computational modelling protocol using the combination of docking, classical (cMD) and accelerated (aMD) molecular dynamics and free energy perturbation (FEP+ protocol) for identification of the binding modes of selected perfluorocarboxyl acids (PFCAs) in the PPARγ nuclear receptor.Initially, we employed both the regular and induced fit docking which failed to correctly predict the ligand binding modes and rank the compounds with respect to experimental free energies of binding, when they were docked into non-native X-ray structure. The cMD and aMD simulations identified the presence of multiple binding modes for these compounds, and the shorter chain PFCAs (C6-C8) continuously moved between a few energetically favourable binding conformations. These re...
AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligan... more AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligands that inhibit the AKT1, as shown by in vitro binding and cell line studies, using a newly designed virtual screening protocol that combines structure-based pharmacophore and docking screens. Taking together with the biological data, the combination of structure based pharamcophore and docking methods demonstrated reasonable success rate in identifying new inhibitors (60-70%) proving the success of aforementioned approach. A detail analysis of the ligand-protein interactions was performed explaining observed activities.<br>
Recent improvements to free energy perturbation (FEP) calculations, especiallyFEP+, established t... more Recent improvements to free energy perturbation (FEP) calculations, especiallyFEP+, established their utility for pharmaceutical lead optimization. However, to dateFEP has typically been helpful only when (1) high-quality X-ray data is available and(2) the target protein does not undergo significant conformational changes. Also, alack of systematic studies on determining an adequate sampling time is often one ofthe primary limitations of FEP calculations. Herein, we propose a modified versionof the FEP/REST (i.e., replica exchange with solute tempering) sampling protocol,based on systematic studies on several targets by probing a large number of permutations with different sampling schemes. Improved FEP+ binding affinity predictions for regular flexible-loop (F-loop) motions and considerable structural changes can be obtained by extending the pre-REST sampling time from 0.24 ns to 5 ns/λand 2×10 ns/λ, respectively. We obtained much more precise ∆∆G calculations of the individual per...
International journal of pharmaceutics, Jan 7, 2018
This project aims to study the nature of interaction and orientation of selected drugs such as de... more This project aims to study the nature of interaction and orientation of selected drugs such as dexamethorphan HBr (DXM), diphenhydramine HCl (DPH), and lidocaine HCl (LDC) inclusion complexes with hydroxyl-propyl ß-cyclodextrin (HP-ß-CD) using HNMR spectroscopy, 2D-NMR ROESY and molecular-modeling techniques. Freeze-drying technique was used to formulate the inclusion complexes between DXM, DPH and LDC with HP-ß-CD (1:1 M ratio) in solid state. Inclusion complex formation was initially characterized by Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. Further characterization of inclusion complexes to determine the interaction of DXM, DPH and LDC with HP-β-CD was performed using the HNMR spectroscopy, 2D-NMR ROESY and molecular modeling techniques. Inclusion complexes of DXM, DPH and LDC with HP-ß-CD were successfully prepared using the freeze-drying technique. Prelimin...
PPARγ activation helix 12 can exist in an antagonist form: evidence from high-throughput accelera... more PPARγ activation helix 12 can exist in an antagonist form: evidence from high-throughput accelerated molecular dynamics and metadynamics.
The interaction of chemokines and their cognate receptors (CCRs) forms a key signaling network de... more The interaction of chemokines and their cognate receptors (CCRs) forms a key signaling network dedicated to promoting an inflammatory tumor microenvironment (TME), leukocyte recruitment and activation, angiogenesis, and growth in all stages of various cancers. Aberrant expressions of chemokines and CCRs are found to correlate with immunosuppression, metastasis, drug resistance, and poor prognosis in breast cancer patients. Several specific inhibitors for chemokines or CCRs are currently tested in clinical trials of multiple cancers. To date, no pan-CCR inhibitor has been developed as a cancer therapy, which is expected to have more clinical advantages than the agent with specificity for a single CCR. We collaborated with Dr. Filip Fratev's team (Micar21, Bulgaria) to develop potent pan-CCR inhibitors for breast cancer. By performing a virtual screen of 4 million compounds based on the analyses of Pharmacophore-based Docking, Induced-fit Docking, Molecular Dynamics, and Metadynam...
In the present study, fifteen benzimidazolyl-2-hydrazones 7a-7o of fluoro-, hydroxy- and methoxy-... more In the present study, fifteen benzimidazolyl-2-hydrazones 7a-7o of fluoro-, hydroxy- and methoxy-substituted benzaldehydes and 1,3-benzodioxole-5-carbaldehyde were synthesized and their structure was identified by IR, NMR, and elemental analysis. The compounds 7j 2-(3-hydroxybenzylidene)-1-(5(6)-methyl-1H-benzimidazol-2-yl)hydrazone and 7i 2-(3-hydroxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazone have exerted the strongest anthelmintic activity (100 % after 24 h incubation period at 37°C) against isolated muscle larvae of Trichinella spiralis in an in vitro experiment. The in vitro cytotoxicity assay towards MCF-7 breast cancer cells and mouse embryo fibroblasts 3T3 showed that the studied benzimidazolyl-2-hydrazones exhibit low to moderate cytotoxic effects. The ability of the studied benzimidazolyl-2-hydrazones to modulate microtubule polymerization was confirmed and suggested that their anthelmintic action is mediated through inhibition of the tubulin polymerization likewise the other known benzimidazole anthelmitics. It was also shown that the four most promising benzimidazolyl-2-hydrazones do not affect significantly the AChE activity even at high tested concentration, thus indicating that they do not have the potential for neurotoxic effects. The binding mode of compounds 7j and 7n in the colchicine-binding site of tubulin were clarified by molecular docking simulations. Taken together, these results demonstrate that for the synthesized benzimidazole derivatives the anthelmintic activity against T. spiralis and the inhibition of tubulin polymerization are closely related.
The mutations in the spike protein of SARS-CoV-2 Omicron variant (B.1.1.529 lineage) gave rise to... more The mutations in the spike protein of SARS-CoV-2 Omicron variant (B.1.1.529 lineage) gave rise to questions, but the data on the mechanism of action at the molecular level is limited. In this study, we present the Free energy of perturbation (FEP) data about the RBD-hACE2 binding of this new variant.We identified two groups of mutations located close to the most contributing substitutions Q498R and Q493R, which altered significantly the RBD-hACE2 interactions. The Q498R, Y505H and G496S mutations, in addition to N501Y, highly increased the binding to hACE2. They enhanced the binding by 98, 14 and 13 folds, respectively, which transforms the S1-RBD to a picomolar binder. However, in contrast to the case in mice the Q493R/K mutations, in a combination with K417N and T478K, dramatically reduced the S1 RBD binding by over 100 folds. The N440K, G446S and T478K substitutions had lesser contribution. Thus, the total effect of these nine mutations located on the interaction surface of RBD-h...
The N501Y and K417N mutations in the spike protein of SARS-CoV-2 and their combination gave rise ... more The N501Y and K417N mutations in the spike protein of SARS-CoV-2 and their combination gave rise to questions, but the data on their mechanism of action at the molecular level were limited. In this study, we present free energy perturbation (FEP) calculations, performed at the end of December 2020, for the interactions of the spike S1 receptor-binding domain (RBD) with both the ACE2 receptor and an antibody derived from COVID-19 patients. Our results showed that the S1 RBD-ACE2 interactions were significantly increased whereas those with the STE90-C11 antibody dramatically decreased. The K417N mutation in a combination with N501Y fully abolished the antibody effect. However, Lys417Asn seems to have a compensatory mechanism of action increasing the S1 RBD-ACE2 free energy of binding. This may explain the increased spread of the virus observed in the U.K. and South Africa and also gives rise to an important question regarding the possible human immune response and the success of the already available vaccines. Notably, when the experimental data became available confirming our calculations, it was demonstrated that protein-protein FEP can be a useful tool for providing urgent data to the scientific community.
The Mu variant of SARS-CoV-2 has been recently classified as a variant of interest (VOI) by the w... more The Mu variant of SARS-CoV-2 has been recently classified as a variant of interest (VOI) by the world health organization (WHO) but limited data are available at the moment. In particular, a special attention was given to the R346K mutation located in the receptor binding domain (RBD). In the current study we performed Free energy of perturbation (FEP) calculations to elucidate it possible impact on a set of neutralizing monoclonal antibodies (mAbs) which have been shown to be strong inhibitors of the most other known COVID-19 variants. Our results show that R346K affects the class 2 antibodies but its effect is not so significant (0.66 kcal/mol); i.e. reduces the binding with RBD about 3 times. An identical value was calculated also in the presence of both class 1 and class 2 antibodies (BD-812/836). Further, a similar reduction in the binding (0.4 kcal/mol) was obtained for BD-821/771 pair of mAbs. For comparison, the addition of K417N mutation, present in the newly registered Mu ...
Benzimidazole anthelmintic drugs hold promise for repurposing as cancer treatments due to their i... more Benzimidazole anthelmintic drugs hold promise for repurposing as cancer treatments due to their interference with tubulin polymerization and depolymerization, manifesting anticancer properties. We explored the potential of benzimidazole compounds with a piperazine fragment at C-2 as tubulin-targeting agents. In particular, we assessed their anthelmintic activity against isolated Trichinella spiralis muscle larvae and their effects on glioblastoma (U-87 MG) and breast cancer (MDA-MB-231) cell lines. Compound 7c demonstrated exceptional anthelmintic efficacy, achieving a 92.7% reduction in parasite activity at 100 μg/mL after 48 hours. In vitro cytotoxicity analysis of MDA-MB 231 and U87 MG cell lines showed that derivatives 7b, 7d, and 7c displayed lower IC50 values compared to albendazole (ABZ), the control. These piperazine benzimidazoles effectively reduced cell migration in both cell lines, with compound 7c exhibiting the most significant reduction, making it a promising candidat...
The N501Y and K417N mutations in spike protein of SARS-CoV-2 and their combination arise question... more The N501Y and K417N mutations in spike protein of SARS-CoV-2 and their combination arise questions but the data about their mechanism of action at molecular level is limited. Here, we present Free energy perturbation (FEP) calculations for the interactions of the spike S1 receptor binding domain (RBD) with both the ACE2 receptor and an antibody derived from COVID-19 patients. Our results shown that the S1 RBD-ACE2 interactions were significantly increased whereas those with the STE90-C11 antibody dramatically decreased; about over 100 times. The K417N mutation had much more pronounced effect and in a combination with N501Y fully abolished the antibody effect. This may explain the observed in UK and South Africa more spread of the virus but also raise an important question about the possible human immune response and the success of already available vaccines.
In recent years, the mammalian GlyT2 transporter have emerged as a promising target for the devel... more In recent years, the mammalian GlyT2 transporter have emerged as a promising target for the development of anti-chronic pain agents. In our current work, we discovered a new set of promising hits that inhibit the glycine transport at nano and micromolar activity and have excellent selectivity over GlyT1 (as shown by in vitro studies), using a newly designed virtual screening (VS) protocol that combines a structure-based pharmacophore and docking screens. Furthermore, the free energy perturbation (FEP+ protocol) calculations and molecular dynamics (MD) studies revealed the GlyT2 amino acid residues critical for the binding and selectivity of both Glycine and our Lead1 compound. The FEP+ results well-matched available literature mutational data proving the quality of generated GlyT2 structure. Based on these calculations we propose that Lead1 may also be a strong inhibitor of the neutral and basic amino acid transporter B (0+) (SLC6A14). Thus, the subsequent lead optimization and char...
Recent improvements to the free energy perturbation (FEP) calculations, especially FEP+ , establi... more Recent improvements to the free energy perturbation (FEP) calculations, especially FEP+ , established their utility for pharmaceutical lead optimization. Herein, we propose a modified version of the FEP/REST (i.e., replica exchange with solute tempering) sampling protocol, based on detail studies on several targets by probing a large number of perturbations with different sampling schemes. Improved FEP+ binding affinity predictions for regular flexible-loop motions and considerable structural changes can be obtained by extending the prior to REST (pre-REST) sampling time from 0.24 ns/λ to 5 ns/λ and 2 × 10 ns/λ, respectively. With this new protocol, much more precise ∆∆G values of the individual perturbations, including the sign of the transformations and decreased error were obtained. We extended the REST simulations from 5 ns to 8 ns to achieve reasonable free energy convergence. Implementing REST to the entire ligand as opposed to solely the perturbed region, and also some import...
Estimating the correct binding modes of ligands in protein-ligand complexes is not only crucial i... more Estimating the correct binding modes of ligands in protein-ligand complexes is not only crucial in the drug discovery process, but also for elucidating potential toxicity mechanisms. In the current paper, we discuss and demonstrate a computational modelling protocol using the combination of docking, classical (cMD) and accelerated (aMD) molecular dynamics and free energy perturbation (FEP+ protocol) for identification of the binding modes of selected perfluorocarboxyl acids (PFCAs) in the PPARγ nuclear receptor.Initially, we employed both the regular and induced fit docking which failed to correctly predict the ligand binding modes and rank the compounds with respect to experimental free energies of binding, when they were docked into non-native X-ray structure. The cMD and aMD simulations identified the presence of multiple binding modes for these compounds, and the shorter chain PFCAs (C6-C8) continuously moved between a few energetically favourable binding conformations. These re...
AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligan... more AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligands that inhibit the AKT1, as shown by in vitro binding and cell line studies, using a newly designed virtual screening protocol that combines structure-based pharmacophore and docking screens. Taking together with the biological data, the combination of structure based pharamcophore and docking methods demonstrated reasonable success rate in identifying new inhibitors (60-70%) proving the success of aforementioned approach. A detail analysis of the ligand-protein interactions was performed explaining observed activities.<br>
Recent improvements to free energy perturbation (FEP) calculations, especiallyFEP+, established t... more Recent improvements to free energy perturbation (FEP) calculations, especiallyFEP+, established their utility for pharmaceutical lead optimization. However, to dateFEP has typically been helpful only when (1) high-quality X-ray data is available and(2) the target protein does not undergo significant conformational changes. Also, alack of systematic studies on determining an adequate sampling time is often one ofthe primary limitations of FEP calculations. Herein, we propose a modified versionof the FEP/REST (i.e., replica exchange with solute tempering) sampling protocol,based on systematic studies on several targets by probing a large number of permutations with different sampling schemes. Improved FEP+ binding affinity predictions for regular flexible-loop (F-loop) motions and considerable structural changes can be obtained by extending the pre-REST sampling time from 0.24 ns to 5 ns/λand 2×10 ns/λ, respectively. We obtained much more precise ∆∆G calculations of the individual per...
International journal of pharmaceutics, Jan 7, 2018
This project aims to study the nature of interaction and orientation of selected drugs such as de... more This project aims to study the nature of interaction and orientation of selected drugs such as dexamethorphan HBr (DXM), diphenhydramine HCl (DPH), and lidocaine HCl (LDC) inclusion complexes with hydroxyl-propyl ß-cyclodextrin (HP-ß-CD) using HNMR spectroscopy, 2D-NMR ROESY and molecular-modeling techniques. Freeze-drying technique was used to formulate the inclusion complexes between DXM, DPH and LDC with HP-ß-CD (1:1 M ratio) in solid state. Inclusion complex formation was initially characterized by Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. Further characterization of inclusion complexes to determine the interaction of DXM, DPH and LDC with HP-β-CD was performed using the HNMR spectroscopy, 2D-NMR ROESY and molecular modeling techniques. Inclusion complexes of DXM, DPH and LDC with HP-ß-CD were successfully prepared using the freeze-drying technique. Prelimin...
PPARγ activation helix 12 can exist in an antagonist form: evidence from high-throughput accelera... more PPARγ activation helix 12 can exist in an antagonist form: evidence from high-throughput accelerated molecular dynamics and metadynamics.
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Papers by Filip Fratev