VMD as a Platform for Interactive Small Molecule Preparation and Visualization in Quantum and Classical Simulations

Modeling and simulation of small molecules such as drugsand biologicalcofactors have been both a major focus of computational chemistryfor decades and a growing need among computational biophysicists whoseek to investigate the interaction of different types of ligandswith biomolecules. Of particular interest in this regard are quantummechanical (QM) calculations that are used to more accurately describesuch small molecules, which can be of heterogeneous structures andchemistry, either in purely QM calculations or in hybrid QM/molecularmechanics (MM) simulations. QM programs are also used to develop MMforce field parameters for small molecules to be used along with establishedforce fields for biomolecules in classical simulations. With thisgrowing need in mind, here we report a set of software tools developedand closely integrated within the broadly used molecular visualization/analysisprogram, VMD, that allow the user to construct, modify, and parametrizesmall molecules and prepare them for QM, hybrid QM/MM, or classicalsimulations. The tools also provide interactive analysis and visualizationcapabilities in an easy-to-use and integrated environment. In thispaper, we briefly report on these tools and their major features andcapabilities, along with examples of how they can facilitate molecularresearch in computational biophysics that might be otherwise prohibitivelycomplex.