Georgios Archontis

Bio: Georgios Archontis is an academic researcher from University of Cyprus. The author has contributed to research in topics: Protein design & Ligand (biochemistry). The author has an hindex of 29, co-authored 58 publications receiving 8460 citations. Previous affiliations of Georgios Archontis include Centre national de la recherche scientifique & National Institutes of Health.

CHARMM: the biomolecular simulation program.

Abstract: CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecu- lar simulation program. It has been developed over the last three decades with a primary focus on molecules of bio- logical interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estima- tors, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numer- ous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983.

Free energy simulations come of age: protein-ligand recognition.

Abstract: In recent years, molecular dynamics simulations of biomolecular free energy differences have benefited from significant methodological advances and increased computer power. Applications to molecular recognition provide an understanding of the interactions involved that goes beyond, and is an important complement to, experimental studies. Poisson-Boltzmann electrostatic models provide a faster and simpler free energy method in cases where electrostatic interactions are important. We illustrate both molecular dynamics and Poisson-Boltzmann methods with a detailed study of amino acid recognition by aspartyl-tRNA synthetase, whose specificity is important for maintaining the integrity of the genetic code.

Enthalpic Contribution to Protein Stability: Insights from Atom-Based Calculations and Statistical Mechanics

Abstract: Publisher Summary This chapter discusses published analyses of protein stability based on model compound data and outlines the assumptions that have been made. The enthalpy of protein folding is considered and a thermodynamic cycle is used to relate the measurements to quantities that can be calculated. The focus is on the enthalpy of denaturation because it is most directly accessible to calculations. The experiments and analysis of Privalov and co-workers, particularly which of Makhatadze and Privalov are considered in detail because these measurements provide the most complete results on the thermodynamics of proteins. The estimates of internal van der Waals and hydrogen bonding contributions to the enthalpy difference between the native and denatured states of the protein are compared with the calculations of the van der Waals and electrostatic terms (the latter includes hydrogen bonding) from an atom-based model. Statistical mechanical calculations and molecular dynamics simulations are used to estimate the difference in solvation enthalpy, as well as the free energy, of the native and unfolded states.

Free energy simulations: the meaning of the individual contributions from a component analysis.

Abstract: A theoretical analysis is made of the decomposition into contributions from individual interactions of the free energy calculated by thermodynamic integration. It is demonstrated that such a decomposition, often referred to as “component analysis,” is meaningful, even though it is a function of the integration path. Moreover, it is shown that the path dependence can be used to determine the relation of the contribution of a given interaction to the state of the system. To illustrate these conclusions, a simple transformation(Cl− to Br− in aqueous solution) is analyzed by use of the Reference Interaction Site Model-Hypernetted Chain Closure integral equation approach; it avoids the calculational difficulties of macromolecular simulation while retaining their conceptual complexity. The difference in the solvation free energy between chloride and bromide is calculated, and the contributions of the Lennard-Jones and electrostatic terms in the potential function are analyzed by the use of suitably chosen integration paths. The model is also used to examine the path dependence of individual contributions to the double free energy differences (ΔΔG or ΔΔA) that are often employed in free energy simulations of biological systems. The alchemical path, as contrasted with the experimental path, is shown to be appropriate for interpreting the effects of mutations on ligand binding and protein stability. The formulation is used to obtain a better understanding of the success of the Poisson-Boltzmann continuum approach for determining the solvation properties of polar and ionic systems. © 1994 Wiley-Liss, Inc.

Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions.

Abstract: We present a new continuum solvation model based on the quantum mechanical charge density of a solute molecule interacting with a continuum description of the solvent. The model is called SMD, where the “D” stands for “density” to denote that the full solute electron density is used without defining partial atomic charges. “Continuum” denotes that the solvent is not represented explicitly but rather as a dielectric medium with surface tension at the solute−solvent boundary. SMD is a universal solvation model, where “universal” denotes its applicability to any charged or uncharged solute in any solvent or liquid medium for which a few key descriptors are known (in particular, dielectric constant, refractive index, bulk surface tension, and acidity and basicity parameters). The model separates the observable solvation free energy into two main components. The first component is the bulk electrostatic contribution arising from a self-consistent reaction field treatment that involves the solution of the nonho...

CHARMM: the biomolecular simulation program.

Abstract: CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecu- lar simulation program. It has been developed over the last three decades with a primary focus on molecules of bio- logical interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estima- tors, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numer- ous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983.

SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules

Abstract: To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.

Gromacs 4.5

Abstract: Motivation: Molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources. Results: Here, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations. Availability: GROMACS is an open source and free software available from http://www.gromacs.org. Contact: erik.lindahl@scilifelab.se Supplementary information:Supplementary data are available at Bioinformatics online.