title: Conformational space of clindamycin studied by ab initio and full-atom molecular dynamics.
abstract: Molecular dynamics (MD) simulations allow determining internal flexibility of molecules at atomic level. Using ab initio Born-Oppenheimer molecular dynamics (BOMD), one can simulate in a reasonable time frame small systems with hundreds of atoms, usually in vacuum. With quantum mechanics/molecular mechanics (QM/MM) or full-atom molecular dynamics (FAMD), the influence of the environment can also be simulated. Here, we compare three types of MD calculations: ab initio BOMD, hybrid QM/MM, and classical FAMD. As a model system, we use a small antibiotic molecule, clindamycin, which is one of the lincosamide antibiotics. Clindamycin acquires two energetically stable forms and we investigated the transition between these two experimentally known conformers. We performed 60-ps BOMD simulations in vacuum, 50-ps QM/MM, and 100-ns FAMD in explicit water. The transition between two antibiotic conformers was observed using both BOMD and FAMD methods but was not noted in the QM/MM simulations.
authors.affiliation: Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Pawińskiego 5A, 02-106, Warsaw, Poland.|College of Inter-faculty Individual Studies in Mathematics and Natural Science, University of Warsaw, Żwirki i Wigury 93, 02-089, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kulczycka-Mierzejewska
authors.affiliation: Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland. joanna@cent.uw.edu.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Trylska
authors.affiliation: Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093, Warsaw, Poland. sadlej@chem.uw.edu.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Sadlej
mesh_terms: D002981:Clindamycin / Q000737:chemistry*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation
chemical_list: D002981:Clindamycin
keywords: Antibiotics; BOMD; Born–Oppenheimer molecular dynamics; Clindamycin; FAMD; Full-atom molecular dynamics; Lincosamides; QM/MM; Quantum mechanics/molecular mechanics