MKTOP: a program for automatic construction of molecular topologies

Abstract

A mecânica molecular é amplamente usada na simulação de biomoléculas. Um arquivo de topologia molecular contendo todos os tipos de átomos, que dependem do ambiente químico, tem de ser construído. MKTOP é um software gratuito capaz de construir topologias moleculares para o GROMACS, sendo assim uma ferramenta útil para seus usuários.Molecular mechanics methods are widely-used for simulations of biomolecules. A molecular topology file containing all atom types, which depend on the chemical environment, must be constructed. MKTOP is a free-software capable of automatic atom type recognition and construction of molecular topologies for GROMACS, being a useful tool for its users. Keywords: molecular mechanics, atom-type recognition, molecular topology, GROMACS, OPLS IntroductionThe use of molecular mechanics (MM) methods in the treatment of biomolecular systems has been increasing steadily. These methods use empirical force fields to calculate interactions between atoms. Applications range from simple geometry optimizations to estimations of binding affinity, molecular dynamics (MD) simulations, among others. GROMACS 1 is one of the most utilized MD software packages and it has the advantage of being free software, distributed under the GNU license. It is able to perform calculations with several force fields, one of them being OPLS-AA.2 This combination is widely-used in protein simulations.In order to set up a MM calculation, one must generate a topology file for the system, in which the connectivities between the atoms and the atom type, which is determined by the concept of chemical function, are specified.Chemical function determination is the major problem to address when creating a topology. Most molecular mechanics softwares have routines for generating a topology, but these are usually only effective for peptides. Although the systems of main interest in the field are proteins, possible inhibitors, co-factors, substrates and agonists may not be peptides. Therefore, automatic routines which successfully identify atom types are extremely helpful to the user. One such routine is called PRODRG 3 , but it is only able to create topologies for united-atom force fields. More recently, a routine named antechamber, 4 capable of creating all-atom molecular topologies, has been included in the last AMBER 5 distribution. However, AMBER is not freely available. Therefore, a program capable of building topologies for GROMACS would be of great appeal.In this paper we report the development of an automatic routine, named MKTOP, to create molecular topologies for GROMACS, utilizing the OPLS-AA force-field. Computational MethodsMKTOP is a user-friendly computational routine written in Perl. A single command line is required to generate a molecular topology. How MKTOP worksThe starting point for constructing a topology is, obviously, a list of the coordinates of all the atoms present in the system; these must be provided to MKTOP in a PDB format file. The atomic charges, which are essential to perform a MM calculation, may be ...

Association of the anti-tuberculosis drug rifampicin with a PAMAM dendrimer

“…These systems were labelled as PAMAM N and PAMAM L , where the subscripts N and L denote a structure appropriate for neutral and low pH conditions, respectively. The corresponding topologies were generated using the MKTOP program [95] and the OPLS-AA force field. [86,87] The OPLS compatible atomic partial charges were generated following the procedure described in Ref.…”

“…Analogously, a structure involving the same number of RIF molecules was chosen for low pH and labelled RIF 20 -PAMAM L . The topology file for the individual RIF molecule was generated using the same procedure as described above for the dendrimer, using the MKTOP program [95], the OPLS-AA force field. [86,87] and the charges according to Ref.…”

Molecular dynamics simulations of the free and inhibitor-bound cruzain systems in aqueous solvent: insights on the inhibition mechanism in acidic pH

“…The construction of the ligand topology was made using MKTOP program (Ribeiro, Horta & de Alencastro, 2008) and the partial charges were calculated at Resp Esp charge Derive (R.E.D.) server (Vanquelef et al, 2011).…”

Evidence of Ternary Complex Formation in Trypanosoma cruzi trans-Sialidase Catalysis

“…III server. Finally, the molecules were parameterized in the Optimized Potentials for Liq-uid Simulation-All Atoms (OPLS/AA) force field (31, 32) with MKTOP software (33).…”