Journal•ISSN: 0920-654X
Journal of Computer-aided Molecular Design
Springer Science+Business Media
About: Journal of Computer-aided Molecular Design is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Docking (molecular) & Virtual screening. It has an ISSN identifier of 0920-654X. Over the lifetime, 2343 publications have been published receiving 104899 citations. The journal is also known as: Computer aided molecular design.
Topics: Docking (molecular), Virtual screening, Quantitative structure–activity relationship, Pharmacophore, Solvation
Papers published on a yearly basis
Papers
More filters
TL;DR: It is shown that database enrichment is improved with proper preparation and that neglecting certain steps of the preparation process produces a systematic degradation in enrichments, which can be large for some targets.
Abstract: Structure-based virtual screening plays an important role in drug discovery and complements other screening approaches. In general, protein crystal structures are prepared prior to docking in order to add hydrogen atoms, optimize hydrogen bonds, remove atomic clashes, and perform other operations that are not part of the x-ray crystal structure refinement process. In addition, ligands must be prepared to create 3-dimensional geometries, assign proper bond orders, and generate accessible tautomer and ionization states prior to virtual screening. While the prerequisite for proper system preparation is generally accepted in the field, an extensive study of the preparation steps and their effect on virtual screening enrichments has not been performed. In this work, we systematically explore each of the steps involved in preparing a system for virtual screening. We first explore a large number of parameters using the Glide validation set of 36 crystal structures and 1,000 decoys. We then apply a subset of protocols to the DUD database. We show that database enrichment is improved with proper preparation and that neglecting certain steps of the preparation process produces a systematic degradation in enrichments, which can be large for some targets. We provide examples illustrating the structural changes introduced by the preparation that impact database enrichment. While the work presented here was performed with the Protein Preparation Wizard and Glide, the insights and guidance are expected to be generalizable to structure-based virtual screening with other docking methods.
3,658 citations
TL;DR: Molden is a software package for pre- and postprocessing of computational chemistry program data that features different options to display MOLecular electronic DENsity, each focusing on a different structural aspect: molecular orbitals, electron density, molecular minus atomic density and the Laplacian of the electron density.
Abstract: Molden is a software package for pre- and postprocessing of computational chemistry program data. Interfacing to the ab initio programs Games-US/UK and Gaussian and to the semi-empirical package MOPAC is provided. The emphasis is on computation and visualization of electronic and molecular properties but, e.g., reaction pathways can be simulated as well. Some molecular properties of interest are processed directly from the output of the computational chemistry programs, others are calculated in MOLDEN before display. The package features different options to display MOLecular electronic DENsity, each focusing on a different structural aspect: molecular orbitals, electron density, molecular minus atomic density and the Laplacian of the electron density. To display difference density, either the spherically averaged atomic density or the oriented ground state atomic density can be used for a number of standard basis sets. The quantum mechanical electrostatic potential or a distributed multiple expansion derived electrostatic potential can be calculated and atomic charges can be fitted to these potentials calculated on Connolly surface(s). Reaction pathways and molecular vibrations can be visualized. Input structures can be generated with a Z-matrix editor. A variety of graphics languages is supported: XWindows, postscript, VRML and Povray format.
2,932 citations
TL;DR: This work focuses on the calculations of vibrational spectra, thermodynamic quantities, isotopic substitution effects, and force constants in a fully integrated program for the study of chemical reactions involving molecules, ions, and linear polymers using MOPAC.
Abstract: Before we start, we need a working definition for MOPAC. The following description has been used many times to describe MOPAC: MOPAC is a general-purpose, semiempirical molecular orbital program for the study of chemical reactions involving molecules, ions, and linear polymers. It implements the semiempirical Hamiltonians MNDO, AM 1, MINDO/3, and MNDOPM3, and combir_es the calculations of vibrational spectra, thermodynamic quantities, isotopic substitution effects, and force constants in a fully integrated program. Elements parameterized at the MNDO level include H, Li, Be, B, C, N, O, F, A1, Si, P, S, C1, Ge, Br, Sn, Hg, Pb, and I; at the PM3 level the elements H, C, N, O, F, A1, Si, P, S, C1, Br, and I are available. Within the electronic part of the calculation, molecular and localized orbitals, excited states up to sextets, chemical bond indices, charges, etc. are computed. Both intrinsic and dynamic reaction coordinates can be calculated. A transition-state location routine and two transition-state optimizing routines are available for studying chemical reactions.
2,422 citations
TL;DR: A simple empirical scoring function designed to estimate the free energy of binding for aprotein–ligand complex when the 3D structure of the complex is known or can be approximated and it is compared to approaches by other workers.
Abstract: This paper describes the development of a simple empirical scoring function designed to estimate the free energy of binding for a protein-ligand complex when the 3D structure of the complex is known or can be approximated. The function uses simple contact terms to estimate lipophilic and metal-ligand binding contributions, a simple explicit form for hydrogen bonds and a term which penalises flexibility. The coefficients of each term are obtained using a regression based on 82 ligand-receptor complexes for which the binding affinity is known. The function reproduces the binding affinity of the complexes with a cross-validated error of 8.68 kJ/mol. Tests on internal consistency indicate that the coefficients obtained are stable to changes in the composition of the training set. The function is also tested on two test sets containing a further 20 and 10 complexes, respectively. The deficiencies of this type of function are discussed and it is compared to approaches by other workers.
1,642 citations
TL;DR: The main features and statistics of the developed system, Virtual Computational Chemistry Laboratory, allowing the computational chemist to perform a comprehensive series of molecular indices/properties calculations and data analysis are reviewed.
Abstract: Internet technology offers an excellent opportunity for the development of tools by the cooperative effort of various groups and institutions. We have developed a multi-platform software system, Virtual Computational Chemistry Laboratory, http://www.vcclab.org, allowing the computational chemist to perform a comprehensive series of molecular indices/properties calculations and data analysis. The implemented software is based on a three-tier architecture that is one of the standard technologies to provide client-server services on the Internet. The developed software includes several popular programs, including the indices generation program, DRAGON, a 3D structure generator, CORINA, a program to predict lipophilicity and aqueous solubility of chemicals, ALOGPS and others. All these programs are running at the host institutes located in five countries over Europe. In this article we review the main features and statistics of the developed system that can be used as a prototype for academic and industry models.
1,377 citations