An Automated Force Field Topology Builder (ATB) and Repository: Version 1.0

Abstract

The Automated force field Topology Builder (ATB, http://compbio.biosci.uq.edu.au/atb ) is a Web-accessible server that can provide topologies and parameters for a wide range of molecules appropriate for use in molecular simulations, computational drug design, and X-ray refinement. The ATB has three primary functions: (1) to act as a repository for molecules that have been parametrized as part of the GROMOS family of force fields, (2) to act as a repository for pre-equilibrated systems for use as starting configurations in molecular dynamics simulations (solvent mixtures, lipid systems pre-equilibrated to adopt a specific phase, etc.), and (3) to generate force field descriptions of novel molecules compatible with the GROMOS family of force fields in a variety of formats (GROMOS, GROMACS, and CNS). Force field descriptions of novel molecules are derived using a multistep process in which results from quantum mechanical (QM) calculations are combined with a knowledge-based approach to ensure compatibility (as far as possible) with a specific parameter set of the GROMOS force field. The ATB has several unique features: (1) It requires that the user stipulate the protonation and tautomeric states of the molecule. (2) The symmetry of the molecule is analyzed to ensure that equivalent atoms are assigned identical parameters. (3) Charge groups are assigned automatically. (4) Where the assignment of a given parameter is ambiguous, a range of possible alternatives is provided. The ATB also provides several validation tools to assist the user to assess the degree to which the topology generated may be appropriate for a given task. In addition to detailing the steps involved in generating a force field topology compatible with a specific GROMOS parameter set (GROMOS 53A6), the challenges involved in the automatic generation of force field parameters for atomic simulations in general are discussed.

A Flexible, Grid-Enabled Web Portal for GROMACS Molecular Dynamics Simulations

“…In this case, the user is responsible for preparing the simulation system. Web portals such as PRODRG, 39 Automated Topology Builder (ATB), 40 SwissParam, 41 and AnteChamber 42 can be used to generate topology and parameter files for nonstandard molecules.…”

Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC

“…The united atom option of GROMOS 54a7 force field (Huang et al 2011;Schmid et al 2011;) was used to calculate the intermolecular and intramolecular interactions for all systems. The DMPC topology was constructed from the Automated Topology Builder (ATB) and repository (Malde et al 2011). The optimized structure of EMH and EM − were obtained though quantum mechanical (QM) calculations with density functional theory (DFT) (Parr and Yang 1994) using the B3LYP exchange-correlation functional (Becke 1993;Imamura et al 2007) and the Pople basis set functions, 6-311++G(d,p) (Ditchfield et al 1971).…”

Missing Fragments: Detecting Cooperative Binding in Fragment-Based Drug Design

“…edu.au/atb). 13 All of the 12 fragments identified by Drinkwater et al 9 contain at least one 5-or one 6-membered aromatic ring. In the structures of the complexes deposited in the PDB, this ring lies sandwiched between the side chains of Phe182 and Asn39 forming a π−π stacking interaction with the side chain of Phe182.…”