Abstract Various molecular interaction networks have been claimed to follow power-law decay for their global connectivity distribution. It has been proposed that there may be underlying generative models that explain this heavy-tailed... more
Abstract Various molecular interaction networks have been claimed to follow power-law decay for their global connectivity distribution. It has been proposed that there may be underlying generative models that explain this heavy-tailed behavior by self-reinforcement processes such as classical or hierarchical scale-free network models.
We present an efficient algorithm for generating semiglobal potential energy surfaces of reactive systems. The method takes as input molecular mechanics force fields for reactants and products and a quadratic expansion of the potential... more
We present an efficient algorithm for generating semiglobal potential energy surfaces of reactive systems. The method takes as input molecular mechanics force fields for reactants and products and a quadratic expansion of the potential energy surface around a small number of geometries whose locations are determined by an iterative process. These Hessian expansions might come, for example, from ab initio electronic structure calculations, density functional theory, or semiempirical molecular orbital theory.
We present an overview of new procedures for including quantum mechanical effects in enzyme kinetics.
We have calculated the reaction rate and kinetic isotope effects for conversion of 2-phospho-d-glycerate to phosphoenolpyruvate by yeast enolase. The potential energy surface is modeled by a combined quantum mechanical/molecular... more
We have calculated the reaction rate and kinetic isotope effects for conversion of 2-phospho-d-glycerate to phosphoenolpyruvate by yeast enolase. The potential energy surface is modeled by a combined quantum mechanical/molecular mechanical method with generalized hybrid orbitals. The dynamics calculations are carried out by semiclassical variational transition state theory with multidimensional tunneling contributions.
We have used canonical variational transition-state theory with multidimensional tunneling contributions (CVT/MT) to calculate 21 kinetic isotope effects (KIE) for the addition of hydrogen atom to ethylene. The potential energies are... more
We have used canonical variational transition-state theory with multidimensional tunneling contributions (CVT/MT) to calculate 21 kinetic isotope effects (KIE) for the addition of hydrogen atom to ethylene. The potential energies are obtained by variable scaling of external correlation (VSEC). The reorientation of the dividing surface (RODS) algorithm is employed so that the same reaction path can be used for every isotopic substitution.
Molecular Interaction Potentials (MIP) are frequently used for the comparison of series of compounds displaying related biological behaviors. These potentials are interaction energies between the considered compounds and relevant probes.... more
Molecular Interaction Potentials (MIP) are frequently used for the comparison of series of compounds displaying related biological behaviors. These potentials are interaction energies between the considered compounds and relevant probes. The interaction energies are computed in the nodes of grids defined around the compounds. There is a need of detailed and objective comparative analyses of MIP distributions in the framework of structure-activity studies.
The temperature dependence of the dynamical bottleneck location for the prototype olefin addition process H+ C2H4 has been studied by variational transition state theory. In addition, a multidimensional tunneling calculation has been... more
The temperature dependence of the dynamical bottleneck location for the prototype olefin addition process H+ C2H4 has been studied by variational transition state theory. In addition, a multidimensional tunneling calculation has been carried out. To obtain a reliable potential energy profile, a new way to extrapolate electronic structure calculations to the limit of full configuration mixing and a complete electronic basis set is proposed.
Background With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio) chemical systems involves a large number of... more
Background With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio) chemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA). The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event.
Abstract The idea that enzymes accelerate their reactions by entropic effects has played a major role in many prominent proposals about the origin of enzyme catalysis. This idea implies that the binding to an enzyme active site freezes... more
Abstract The idea that enzymes accelerate their reactions by entropic effects has played a major role in many prominent proposals about the origin of enzyme catalysis. This idea implies that the binding to an enzyme active site freezes the motion of the reacting fragments and eliminates their entropic contributions,(ΔS cat‡)′, to the activation energy. It is also implied that the binding entropy is equal to the activation entropy,(ΔS w‡)′, of the corresponding solution reaction.
Several people contributed to the development and improvement of ByoDyn. ByoDyn is a joint effort from the Computational Biochemistry and Biophysics Laboratory. It is an original idea from Jordi Villai Freixa and Adrián López Garcıa de... more
Several people contributed to the development and improvement of ByoDyn. ByoDyn is a joint effort from the Computational Biochemistry and Biophysics Laboratory. It is an original idea from Jordi Villai Freixa and Adrián López Garcıa de Lomana. Essential contributions were implemented byAlex Gómez who improved most of the software functionalities (SBML compatibility, sensitivity analysis, identifiability analysis and other issues) and Miguel Hernández who implemented the parallel code.
Abstract: MC-TINKERATE is a computer program for carrying out calculations of chemical reaction rates of polyatomic species by using single-configuration molecular mechanics (SCMM) methods or multi-configuration molecular mechanics (MCMM)... more
Abstract: MC-TINKERATE is a computer program for carrying out calculations of chemical reaction rates of polyatomic species by using single-configuration molecular mechanics (SCMM) methods or multi-configuration molecular mechanics (MCMM) methods available in MCTINKER to calculate the potential energy surface and by using POLYRATE for the dynamics. The interface between POLYRATE and MC-TINKER is based on the POLYRATE hooks protocol.
ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i... more
ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel· lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora.
Abstract. In this paper we propose a method for carrying out variational transition state theory calculations without first obtaining a converged minimum-energy path (MEP). We illustrate the method in two ways, first of all by employing... more
Abstract. In this paper we propose a method for carrying out variational transition state theory calculations without first obtaining a converged minimum-energy path (MEP). We illustrate the method in two ways, first of all by employing an unconverged MEP and secondly by using a dynamically optimized distinguished reaction path. Preliminary tests of the algorithm for the reactions OH+ H 2→ H 2 O+ H and C 2 H 5→ C 2 H 4+ H are very encouraging.
1Faculty of Engineering and Architecture, Universidad Católica de Manizales, Manizales, Colombia, arincons@ucm.edu.co 2Departament of Physics and Mathematics, Universidad Autónoma de Manizales, Manizales, Colombia, jvilla@autonoma.edu.co... more
1Faculty of Engineering and Architecture, Universidad Católica de Manizales, Manizales, Colombia, arincons@ucm.edu.co 2Departament of Physics and Mathematics, Universidad Autónoma de Manizales, Manizales, Colombia, jvilla@autonoma.edu.co 3Department of Electrical and Electronics Engineering & Computer Science, Universidad Nacional de Colombia, Cra 27 No.
The new RODS algorithm based on optimizing the orientation of the dividing suface at each point along the reaction path in order to maximize the free energy of the generalized transition state containing that point has been used to carry... more
The new RODS algorithm based on optimizing the orientation of the dividing suface at each point along the reaction path in order to maximize the free energy of the generalized transition state containing that point has been used to carry out variational transition state calculations and tunneling calculations for two reactions with high-frequency vibrations strongly coupled to the reaction coordinate,(Cl-)(CH3NH3+)→ ClCH3 (NH3) and ClCH3+ NH3, and CH3Cl (H2O)+ NH3 (H2O)→(CH3NH3+)(Cl-)(H2O) 2.
Abstract The Virtual Physiological Human (VPH) is a major European e-Science initiative intended to support the development of patient-specific computer models and their application in personalized and predictive healthcare. The VPH... more
Abstract The Virtual Physiological Human (VPH) is a major European e-Science initiative intended to support the development of patient-specific computer models and their application in personalized and predictive healthcare. The VPH Network of Excellence (VPH-NoE) project is tasked with facilitating interaction between the various VPH projects and addressing issues of common concern.
Abstract. In this minireview we summarize the characteristics of 9 different use cases prototypical of complex systems simulations. Problems like social behavior, gene regulatory networks, molecular simulations and supply chain all share... more
Abstract. In this minireview we summarize the characteristics of 9 different use cases prototypical of complex systems simulations. Problems like social behavior, gene regulatory networks, molecular simulations and supply chain all share a common structure. They can be classified according to their computational needs in a way suitable for implementation in a quasiopportunistic environment as the one provided by the QosCos-Grid project.
Abstract: MC-TINKERATE is a computer program for carrying out calculations of chemical reaction rates of polyatomic species by using single-configuration molecular mechanics (SCMM) methods or multi-configuration molecular mechanics (MCMM)... more
Abstract: MC-TINKERATE is a computer program for carrying out calculations of chemical reaction rates of polyatomic species by using single-configuration molecular mechanics (SCMM) methods or multi-configuration molecular mechanics (MCMM) methods available in MCTINKER to calculate the potential energy surface and by using POLYRATE for the dynamics. The interface between POLYRATE and MC-TINKER is based on the POLYRATE hooks protocol.
Currently there is no formal VPH-specific training in Europe [1]. Some Masters programmes in related areas partially address this challenge, but none focuses on the essential characteristics of the discipline, such as heterogeneous data... more
Currently there is no formal VPH-specific training in Europe [1]. Some Masters programmes in related areas partially address this challenge, but none focuses on the essential characteristics of the discipline, such as heterogeneous data fusion, multi-scale and multi-physics modelling of physiopathology, and simulation of complex clinical work-flows. The VPH-MIP project addresses this deficiency by developing a framework for VPH graduate programmes. Fig.
Note: The version number of CRATE is 9.0. 1. This means that CRATE–version 9.0. 1 is based on POLYRATE–version 9.0. The interface of CHARMM–versions c28b1 to c28b2 with POLYRATE–version 9.0 will result in CHARMMRATE–1.0, whereas the... more
Note: The version number of CRATE is 9.0. 1. This means that CRATE–version 9.0. 1 is based on POLYRATE–version 9.0. The interface of CHARMM–versions c28b1 to c28b2 with POLYRATE–version 9.0 will result in CHARMMRATE–1.0, whereas the interface of CHARMM–version c28b3 and later with POLYRATE–version 9.0 gives CHARMMRATE–2.0.
Background To enhance our understanding of complex biological systems like diseases we need to put all of the available data into context and use this to detect relations, pattern and rules which allow predictive hypotheses to be defined.... more
Background To enhance our understanding of complex biological systems like diseases we need to put all of the available data into context and use this to detect relations, pattern and rules which allow predictive hypotheses to be defined. Life science has become a data rich science with information about the behaviour of millions of entities like genes, chemical compounds, diseases, cell types and organs, which are organised in many different databases and/or spread throughout the literature.
The vertebrate otic placode is a transient embryonic structure that gives rise to the inner ear. This structure is composed of around 1000 cells where several genes are expressed in different domains. These early expression patterns... more
The vertebrate otic placode is a transient embryonic structure that gives rise to the inner ear. This structure is composed of around 1000 cells where several genes are expressed in different domains. These early expression patterns position the structures that, later on, will differentiate into diverse cell types or sensory organs necessary for hearing and balance.
The cystic fibrosis transmembrane conductance regulator (CFTR) is an unusual ABC transporter, functioning as a chloride channel critical for fluid homeostasis in multiple organs. Disruption of CFTR function is associated with cystic... more
The cystic fibrosis transmembrane conductance regulator (CFTR) is an unusual ABC transporter, functioning as a chloride channel critical for fluid homeostasis in multiple organs. Disruption of CFTR function is associated with cystic fibrosis making it an attractive therapeutic target. In addition, CFTR blockers are being developed as potential anti-diarrheals. CFTR drug discovery is hampered by the lack of high resolution structural data and considerable efforts have been invested in modeling the channel structure.
Summary Alzheimer's disease neuropathology is characterized by neuronal death, amyloid β-peptide deposits and neurofibrillary tangles composed of paired helical filaments of tau protein. Although crucial for our understanding of the... more
Summary Alzheimer's disease neuropathology is characterized by neuronal death, amyloid β-peptide deposits and neurofibrillary tangles composed of paired helical filaments of tau protein. Although crucial for our understanding of the pathogenesis of Alzheimer's disease, the molecular mechanisms linking amyloid β-peptide and paired helical filaments remain unknown.
Abstract Information coming from omics disciplines is currently fragmented, and frequently the lack of appropriate tools for their integration into global models severely limits progress in the understanding of the underlying mechanisms... more
Abstract Information coming from omics disciplines is currently fragmented, and frequently the lack of appropriate tools for their integration into global models severely limits progress in the understanding of the underlying mechanisms of complex chronic disorders. EC-funded BioBridge project (FP6-2005-LIFESCIHEALTH-7 037909, http://www. biobridge. eu) focusses on the creation of systemic dynamical models to link molecular mechanisms to complex diseases.