[Methods of computer-assisted molecular modeling]. 1998

G Náray-Szabó
ELTE TTK Elméleti Kémiai Tanszék, Budapest.

We present an overview on modern computer methods of molecular modelling. After treating three main steps of drug evaluation, namely target identification, lead identification and lead optimisation, we shortly discuss molecular graphics, molecular mechanics, molecular orbital and molecular dynamics methods. These are suitable for the more-or-less adequate modelling of real molecular processes both at the microscopic and the macroscopic levels. Molecular graphics provides beautiful pictures for the specialist that allow inspection and manipulation of detailed molecular models. An especially useful tool for the visualisation of molecular entities is the display of various properties on the molecular surface that allows rapid recognition of important relationships. Molecular mechanics is able to predict properties (e.g. geometric parameters, conformer stability) of several classes of molecules with an accuracy close to the experimental one, therefore it plays an important role in complementing molecular graphics. The performance of molecular orbital methods increased considerably in the last decade thus we can calculate parameters for isolated or interacting molecules that are not easily amenable to experiment (e.g. structure and energetics of unstable species or activation energies of elementary processes). Computer simulation methods provide a link between gas-phase models of microscopic structures or processes and macroscopic properties or events that may be derived from the former. Thus, it became possible to apply computerised methods for an adequate simulation of important events, like chemical and biochemical reactions, drug-target interactions, drug delivery and the similar that determine drug action. It is stressed that the hardware and software for computer-aided molecular modelling may not be absent from the arsenal of a drug designer.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D003196 Computer Graphics The process of pictorial communication, between human and computers, in which the computer input and output have the form of charts, drawings, or other appropriate pictorial representation. Computer Graphic,Graphic, Computer,Graphics, Computer
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D017433 Protein Structure, Secondary The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation. Secondary Protein Structure,Protein Structures, Secondary,Secondary Protein Structures,Structure, Secondary Protein,Structures, Secondary Protein

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