Parametrization of 2-thiouracil and 4-thiouracil in CHARMM all-atom empirical force field

Abstract

A new set of force field parameters complementing the CHARMM27 all atom empirical force field for nucleic acids was developed for 2-thiouracil and 4-thiouracil, two naturally modified RNA bases. The new parameters allow for molecular modeling and molecular dynamics simulations of RNA containing 2-thiouracil and 4-thiouracil. Over the last several years, the main goal of molecular biology became the understanding of the functions of biological molecules in terms of structure, interactions and processes at the atomic level. Beside the experimental techniques, computer modeling and simulations, providing information at atomic level and enhancing the interpreta- tion of the biophysical and biochemical experimental data are widely used in the study of biomolecules. Despite the extremely fast progress of computing power, such cal- culations have to be based on a compromise between the complexity of the description of the molecular system, the number of atoms included, and the computational time required for a reliable description of the investigated process. The most efficient and commonly used in studies of large and complex biological systems are the techniques based on empirical force field. The force field comprises the potential energy function U(R) and parameters (1). The potential energy function is a mathematical equation which allows calculating the potential energy as a function of three-dimensional structure. Parameters are related to the chemical structure of studied molecule. The force field describes entire classes of the molecules with compromised accuracy, as an extrapolation from the empirical data of a representative set of molecules. The majority of biomolecular simulations were per- formed with CHARMM (2, 3) or AMBER (4) program. The force fields developed within these programs are re- ferred to as CHARMM and AMBER force field, respec- tively.