Brownian dynamics of interactions between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mutants and F-actin

Brownian dynamics simulations of computer models of GAPDH mutants interacting with F-actin emphasized the electrostatic nature of such interactions, and confirmed the importance of four previously identified lysine residues on the GAPDH structure (Ouporov, I.V.; Knull, H.R.; Lowe, S.L.; Thomasson, K.A. J Mol Recognit 2001, 14, 29-41) in these interactions. Mutants were GAPDH models in which one or more of the previously identified lysines had been replaced with alanine. Simulations showed reduced binding of these mutants to F-actin compared to wild-type GAPDH. Binding was significantly reduced by mutating the four lysines; the specific electrostatic interaction energy of the quadruple mutant was -7.3 (plus-minus) 1.0 compared to -11.4 (plus-minus) 0.5 kcal/mol for the wild enzyme. The BD simulations also reaffirmed the importance of quaternary structure for GAPDH binding F-actin.