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Sarzyńska J.

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CHARMM, force field, nucleic acids, 2-thiouracil, 4-thiouracil, molecular dynamics, quantum mechanical calculations1. INTRODUCTIONOver the last several years, the main goal of molecularbiology became the understanding of the functions ofbiological molecules in terms of structure, interactions andprocesses at the atomic level. Beside the experimentaltechniques, computer modeling and simulations, providinginformation at atomic level and enhancing the interpretationof the biophysical and biochemical experimental dataare widely used in the study of biomolecules. Despitethe extremely fast progress of computing power, such calculationshave to be based on a compromise betweenthe complexity of the description of the molecular system,the number of atoms included, and the computational timerequired for a reliable description of the investigatedprocess.The most efficient and commonly used in studies oflarge and complex biological systems are the techniquesbased on empirical force field. The force field comprisesthe potential energy function U(R) and parameters [1]. Thepotential energy function is a mathematical equation whichallows calculating the potential energy as a function ofthree-dimensional structure. Parameters are related to thechemical structure of studied molecule. The force fielddescribes entire classes of the molecules with compromisedaccuracy, as an extrapolation from the empirical data of arepresentative set of molecules.The majority of biomolecular simulations were performedwith CHARMM [2, 3] or AMBER [4] program.The force fields developed within these programs are referredto as CHARMM and AMBER force field, respectively.The potential energy for the CHARMM force field hasa form:( ) ( )( ) ( ( ))( )2 20 UB 0bonds UB20angle dihedrals20impropers12 6min minnonbonded( )1 cos.ƒĆ ƒÔ.ƒĆ ƒĆ ƒÔ ƒÂ. .ƒĂ= . + . ++ . + + . ++ . +. .. . . . . . + . .. . . . . . + . .. .. . . . . .. . . . . . . .ƒ° ƒ°ƒ° ƒ°ƒ°ƒ° ij ijbi jijij ij D ijU R K b b K S SK K nKR R q qr r . rThe optimized parameters are equilibrium values ofbond length, b0, Urey-Bradley 1.3 distance, S0, valenceangle, ƒĆ0, improper torsion angle, ƒÓ0, and force constants ofbond, Kb, Urey-Bradley, KUB, valence angle, KƒĆ, dihedralangles, KƒÔ, and improper torsion angle, KƒÓ. The parametersn and ƒÂ in the dihedral term are the multiplicity and phase,respectively. These terms are referred to as internal parameters.Nonbonded parameters including partial atomiccharges, qi, the Lennard-Jones (LJ) well depth, ƒĂij, andminimum interaction radius, minij R are also optimized. Theforce field parameters are adjusted to simultaneously reproducesmall molecule target data obtained from quantummechanical (QM) calculations and experiments and experimentalresults for nucleic acid oligomers, e.g., condensedphase structural properties of DNA and RNA.The most recent CHARMM force field for nucleic acidsis CHARMM27

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.

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