DISTAL RESIDUE CO INTERACTION IN CARBONMONOXY MYOGLOBINS - A MOLECULAR-DYNAMICS STUDY OF 3 DISTAL MUTANTS

Six 90-ps molecular dynamics trajectories, two for each of three dista l mutants of sperm whale carbonmonoxy myoglobin, are reported; solvent waters within 16 Angstrom of the active site nave been included In bo th His64Gln trajectories, the distal side chain remains part of the he me pocket, forming a ''closed'' conformation similar to that of the wi ld type 64N(delta)H tautomer. Despite a connectivity more closely rese mbling the NepsilonH histidine tautomer, close interactions with the c arbonyl ligand similar to those observed for the wild type 64N(epsilon )H tautomer are prevented in this mutation by repulsive interactions b etween the carbonyl O and the 64O(epsilon). The aliphatic distal side chain of the His64Leu mutant shows little interaction with the carbony l ligand in either His64Leu trajectory. Solvent water molecules move i nto and out the active site in the His64Gly mutant trajectories; durin g all the other carbonmonoxy myoglobin trajectories, including the wil d type distal tautomers considered in an earlier work, solvent molecul es rarely encroach closer than 6 Angstrom of the active site. These re sults are consistent with a recent structural interpretation of the wi ld type infrared spectrum, and the current reinterpretation that the d istal-ligand interaction in carbonmonoxy myoglobin is largely electros tatic, not steric, in nature.