Multicanonical Monte Carlo calculation of the free-energy map of the base-amino acid interaction

The specific interactions between base pairs and amino acids were studied b y the multicanonical Monte Carlo method. We sampled numerous interaction co nfigurations and side-chain conformations of the amino acid by the multican onical algorithm, and calculated the free energies of the interactions betw een an amino acid at given C-alpha positions and a fixed base pair. The con tour maps or free energy derived from this calculation represent the prefer red C-alpha position of the amino acid around the base, and these mars of v arious combinations of bases and amino acids can be used to quantify the sp ecificity of intrinsic base-amino acid interactions. Similarly, enthalpy an d entropy mars will provide further details of the specific interactions. W e have also calculated the free-energy map of the orientations of the C-alp ha-C-beta bond vector, which indicates the preferential orientation of the amino acid against the base. We compared the results obtained by the multic anonical method with those of the exhaustive sampling and canonical Monte C arlo methods. The free-energy map of the base-amino acid interaction obtain ed by the multicanonical simulation method was nearly identical to the accu rate result derived from the exhaustive sampling method. This indicates tha t a single multicanonical Monte Carlo simulation can produce an accurate fr ee-energy map. Multicanonical Monte Carlo sampling produced free-energy map s that were more accurate than those produced by canonical Monte Carlo samp ling. Thus, the multicanonical Monte Carlo method can serve as a powerful t ool for estimating the free-energy landscape of base-amino acid interaction s and for elucidating the mechanism by which amino acids of proteins recogn ize particular DNA base pairs. (C) 2000 John Wiley & Sons, Inc.