Testing simplified protein models of the hPin1 WW domain

¹ Istituto di Fisica della Materia (INFM)
² Centro Interdip. per lo studio delle dinamiche complesse
³ Università di Firenze (Dip. di Fisica)

^* To whom correspondence should be addressed. E-mail: cecconif{at}roma1.infn.it.

Submitted on June 22, 2005
Revised on August 15, 2005
Accepted on 6 April 2006

	Abstract

The WW domain of the human Pin1 protein for its simple topology and the large amount of experimental data is an ideal candidate to assess theoretical approaches to protein folding. The purpose of the present work is to compare the reliability of the chemically-based Sorenson/Head-Gordon (SHG) model and a standard native centric model in reproducing through molecular dynamics simulations some of the well known features of the folding transition of this small domain. Our results show that the Go model correctly reproduces the cooperative, two-state, folding mechanism of the WW-domain, while the SHG model predicts a transition occurring in two stages: a collapse followed by a structural rearrangement. The lack of a cooperative folding in the SHG simulations appears to be related to the non-funnel shape of the energy landscape featuring a partitioning of the native valley in sub-basins corresponding to different chain chiralities. However the SHG approach remains more reliable in estimating the -values with respect to Go-like description. This may suggest that the WW-domain folding process is stirred by energetic and topological factors as well, and it highlights the better suitability of chemically-based models in simulating mutations.

Key Words: Phi-values, WW-domains, coarse-grained models, cooperativity, folding

This article has been cited by other articles:

				C. Guardiani, F. Cecconi, and R. Livi Stability and Kinetic Properties of C5-Domain from Myosin Binding Protein C and its Mutants Biophys. J., February 15, 2008; 94(4): 1403 - 1411. [Abstract] [Full Text] [PDF]

				Z. Luo, J. Ding, and Y. Zhou Temperature-Dependent Folding Pathways of Pin1 WW Domain: An All-Atom Molecular Dynamics Simulation of a Go Model Biophys. J., September 15, 2007; 93(6): 2152 - 2161. [Abstract] [Full Text] [PDF]