Secondary structure, mechanical stability and location of transition state of proteins

¹ Institute of Physics, Polish Academy of Sciences

^* To whom correspondence should be addressed. E-mail: masli{at}ifpan.edu.pl.

Submitted on February 8, 2007
Revised on April 15, 2007
Accepted on 11 June 2007

	Abstract

It is well known that the unfolding times of proteins, _µ, scales with the external mechanical force f as _µ = _µ⁰\exp(-f _µ/k_BT), where _µ is the location of the average transition state along the reaction coordinate given by the end-to-end distance. Using the off-lattice Go-like models, we have shown that in term of _µ proteins may be divided into two classes. The first class which includes - and /-proteins, has _µ 2-5Å while the second class of -proteins has _µ about three times larger than that of the first class, _µ 7-15Å. These results are in good agreement with the experimental data. The secondary structure is found to play the key role in determining the shape of the free energy landscape. Namely, the distance between the native state and the transition state depends on the helix content linearly. It is shown that _µ have strong correlation with mechanical stability of proteins. Defining the unfolding force, fµ, from the constant velocity pulling measurements as a measure of the mechanical stability, we predict that _µ decays with fµ by a power law, _µ ~fµ^-µ, where the exponent µ 0.4. We have demonstrated that the unfolding force correlates with the helix content of a protein. The contact order, which is a measure of fraction of local contacts, was found to strongly correlate with the mechanical stability and the distance between the transition state and native state. Our study reveals that _µ and fµ might be estimated using either the helicity or the contact order.

Key Words: Go modeling, Langevin dynamics, mechanical stability, protein unfolding, secondary structure, transition state