Kinetics of internal-loop formation in polypeptide chains: a simulation study

¹ University of Florida

^* To whom correspondence should be addressed. E-mail: sjhagen{at}ufl.edu.

Submitted on June 28, 2006
Revised on September 21, 2006
Accepted on 28 November 2006

	Abstract

The speed of simple diffusional motions, such as the formation of loops in the polypeptide chain, places one physical limit on the speed of protein folding. Many experimental studies have explored the kinetics of formation of end-to-end loops in polypeptide chains; however, protein folding more often requires the formation of contacts between interior points on the chain. One expects that, for loops of fixed contour length, interior loops will form more slowly than end-to-end loops, owing to the additional excluded volume associated with the "tails". We estimate the magnitude of this effect by generating ensembles of randomly coiled, freely jointed chains, and then using the theory of Szabo et al. (1980) to calculate the corresponding contact formation rates for these ensembles. Adding just a few residues, to convert an end-to-end loop to an internal loop, sharply decreases the contact rate. Surprisingly, the relative change in rate increases for a longer loop; sufficiently long tails, however, actually reverse the effect and accelerate loop formation slightly. Our results show that excluded volume effects in real, full-length polypeptides may cause the rates of loop formation during folding to depart significantly from the values derived from recent loop formation experiments on short peptides.

Key Words: Brownian movement, chain dynamics, intrachain diffusion, polymers, protein folding