Babak Khalili Hadad

Each daughter cell has to receive the correct complement of chromosomes in mitosis. Some of mitotic kinases are critical to manage individualization of chromosomes. Haspin is newly discovered kinase with regulatory effect. Haspin protein has serine/ threonine kinase activity. Thr 3 of Histone H3 is the only substrate of Haspin to do phosphorylation. Highly potent and selective ligands are developed using organo non-metallic inhibitors. Non- metal centers prepare a big chemical chamber. Uncontrolled growth, survival and metastasis are some characteristics of cancer. These are caused because of perturbation of regulatory signaling pathways specially, kinases. Chemicals specifically inhibits such regulators, are targets for chemotherapy. Haspin (PDB ID: 3IQ7) is analyzed in present research. H-bond and Hydrophobic pocket interactions are studied with both docking and ONIOM methods. 5- Iodotubercidin-the mimetic structure of ATP- is one of effective inhibitors. To increase the efficacy and its attraction to binding site of the Haspin, it is suggested to modify the structure of drug to increase H-bond attraction. The main engaged amino acids in binding site that are responsible to produce H- bonds, are Glu606, Gly608, Asp611 and Gly653 .By modifying the drug it is possible to increase some sites, to engage more amino acids, close to present pocket.  Gln614, Arg616 are closest functional amino acids based on primary structure. The same process will be done for hydrophobic pocket where Ile490, Gly491, Val498, Ala509, Phe 609, Leu656, and Ile 686 are the main amino acids. Phe495, Phe499, Ile685, Val508 and Phe605 are suggested to be the next targets. Oxygen and Fluorine are found more effective than Iodine to make the system more stable. It is suggested to use the Oxygen or Fluorine as two electronegative elements instead of the Iodine.

Each daughter cell has to receive the correct complement of chromosomes in mitosis. Some of mitotic kinases are critical to manage individualization of chromosomes. Haspin is newly discovered kinase with regulatory effect. Haspin protein has serine/ threonine kinase activity. Thr 3 of Histone H3 is the only substrate of Haspin to do phosphorylation. Highly potent and selective ligands are developed using organo non-metallic inhibitors. Non- metal centers prepare a big chemical chamber. Uncontrolled growth, survival and metastasis are some characteristics of cancer. These are caused because of perturbation of regulatory signaling pathways specially, kinases. Chemicals specifically inhibits such regulators, are targets for chemotherapy. Haspin (PDB ID: 3IQ7) is analyzed in present research. H-bond and Hydrophobic pocket interactions are studied with both docking and ONIOM methods. 5- Iodotubercidin-the mimetic structure of ATP- is one of effective inhibitors. To increase the efficacy and its attraction to binding site of the Haspin, it is suggested to modify the structure of drug to increase H-bond attraction. The main engaged amino acids in binding site that are responsible to produce H- bonds, are Glu606, Gly608, Asp611 and Gly653 .By modifying the drug it is possible to increase some sites, to engage more amino acids, close to present pocket.  Gln614, Arg616 are closest functional amino acids based on primary structure. The same process will be done for hydrophobic pocket where Ile490, Gly491, Val498, Ala509, Phe 609, Leu656, and Ile 686 are the main amino acids. Phe495, Phe499, Ile685, Val508 and Phe605 are suggested to be the next targets. Oxygen and Fluorine are found more effective than Iodine to make the system more stable. It is suggested to use the Oxygen or Fluorine as two electronegative elements instead of the Iodine.

To design self-assembly nanocarrier to maintain a particular biological function is the main goal of bionanobiology. Biodegradable and biocompatible materials are more preferred to prevent the polymer remaining in the body, in the preparation of particles for drug delivery purpose. An advantage of particles that are produced based on proteins is that, not only they are safe in biological purposes, but also they contain functional -COOH and -NH2 groups, the effective cross linking agents. It is important to make the couple nano ring system more stable with a nanoplymer with biocompatibility, low cost, high performance and lightweight such as poly(lactic acid). The heterocyclic nanorings were designed with three constant members of glycine and three variable amino acid members. The effect of Poly-L-lactate chain was introduced as the main biodegradable, and easy to produce and use nano support. All systems were analyzed physicochemically by computational methods. Temperature as the mail surrounding r effect is considered in this investigation. Geometrical changes in order to increase temperature may cause the rings near each others, to form a new geometrical optimization and attract each other more. The results considered that, different utilization for various drugs structure, with any type of hydrophobicity or hydrophilicity, any dipole moment, suitable couple rings based on the obtained results, could be designed. Poly electrolytes such as polylactic acid (PLA) make the systems more strong, to deliver a pack of drugs, for example in production of arterial stents.

Formation of bone outside the skeletal system which can occur in all kinds of soft tissues is called Ectopic or Heterotopic Ossification (HO). It is the abnormal formation of true bone within extra skeletal soft tissues. The TGF-β super family several physiological processes are mediate by these polypeptides such as regulates bone formation and resorption as well as osteoclasts differentiation and survival is stimulated by them. Total of 21 head injured patients admitted in the hospital between 8 to 33 years old. All individuals are treated with indomethacin to control HO formation. The red light treatment and heat lamp exposure were done for 20 min in each day of physiotherapy. Both effective members of transforming growth factor- β, superfamily were analyzed by molecular mechanic methods in amber force field. Montecarlo simulation was done for 200 pSec and the ψ, φ angles of each amino acids were calculated. Clinically, of 25 potentially relevant records identified, 21 were related to HO. Following the treatment, 11 individuals showed the response to heat exposure and physical exercises. 9 out of 21 not only never do effective response to heat treatment, but also progress the HO formation. The results reveal that 2 tgi tends to arrange the protein critical angels of φ and ψ, into more favored and/ or allowed region and the formation and development of right handed, left handed α- helices and β- pleated sheath will be more facilitated because of rising in temperature. It is suggested that this phenomenon cause 2tgi to act in a better thermodynamic situation.

Bone morphogenetic proteins (BMPs) induce bone formation and healing. Bone can form in extraskeletal tissue in response to trauma and elevating BMPs. Several BMPs stimulated to increase due to neuroprotective effect. To get the injured zone of fraction warm is one of the suggested methods to prevent heterotopic ossification (HO). But about half of patients get the worst clinical situation. Montecarlo simulation was done with Hyperchem 8 and Ramachandran plot were designed with VMD 1.8.2. pdb files of both 1 tfg and 2 tgi proteins were selected from Protein Data Bank. φ and ψ of all 110 amino acid were calculated in both proteins after Montecarlo simulation at 290, 310 and 315 K for 200 ps, surrounded by water. 1 tfg is affected by increasing the temperature. The favored and allowed regions were decreased in population of dihedral angles. Increasing the temperature more than room temperature can cause more allowed dihedrals for 2 tgi. It is suggested that utilization of thermogenerator lamp progress the HO in such patients.

Ab initio (RHF/STO-3G) quantum chemical calculations using the self-consistent reaction field (SCRF) model were carried out to analyze the effect of solvent polarity on the relative Gibbs free energies, the dipole moments, and the structural stability of peptide macrocycles based on unsubstituted cyclo[Gly6] and its trisubstituted derivatives containing Me, NH2, or OH groups at the Cα atom. The macrocycles studied are stable in water at both room temperature and at body fever temperature, which is important for the design of a stable nanovehicle for drug delivery in water.

126 Chiang Mai, Thailand–August 4-6, 2010 http://www. icsst2010. fa. itb. ac. id Proceeding of The 1st International Conference on Computational for Science and Copyright© 2010 ITB-CMU-IAU Computational study of DNA interaction with carbon nanotube and ...