Wenwei Zheng

Learn More
There has been a long-standing controversy regarding the effect of chemical denaturants on the dimensions of unfolded and intrinsically disordered proteins: A wide range of experimental techniques suggest that polypeptide chains expand with increasing denaturant concentration, but several studies using small-angle X-ray scattering (SAXS) have reported no(More)
We present a multiscale method for the determination of collective reaction coordinates for macromolecular dynamics based on two recently developed mathematical techniques: diffusion map and the determination of local intrinsic dimensionality of large datasets. Our method accounts for the local variation of molecular configuration space, and the resulting(More)
The long-timescale dynamics of macromolecular systems can be oftentimes viewed as a reaction connecting metastable states of the system. In the past decade, various approaches have been developed to discover the collective motions associated with this dynamics. The corresponding collective variables are used in many applications, e.g., to understand the(More)
Chondrocyte apoptosis triggered by endoplasmic reticulum (ER) stress plays a vital role in the pathogenesis of osteoarthritis (OA). Bushen Zhuangjin decoction (BZD) has been widely used in the treatment of OA. However, the cellular and molecular mechanisms responsible for the inhibitory effects of BZD on chondrocyte apoptosis remain to be elucidated. In the(More)
Chemical denaturants are the most commonly used agents for unfolding proteins and are thought to act by better solvating the unfolded state. Improved solvation is expected to lead to an expansion of unfolded chains with increasing denaturant concentration, providing a sensitive probe of the denaturant action. However, experiments have so far yielded(More)
The gap between the time scale of interesting behavior in macromolecular systems and that which our computational resources can afford often limits molecular dynamics (MD) from understanding experimental results and predicting what is inaccessible in experiments. In this paper, we introduce a new sampling scheme, named diffusion-map-directed MD (DM-d-MD),(More)
Several methods have been developed in the past few years for the analysis of molecular dynamics simulations of biological (macro)molecules whose complexity is difficult to capture by simple projections of the free-energy surface onto one or two geometric variables. The locally scaled diffusion map (LSDMap) method is a nonlinear dimensionality reduction(More)
A recent study on the dynamics of polymer reversal inside a nanopore by Huang and Makarov [J. Chem. Phys. 128, 114903 (2008)] demonstrated that the reaction rate cannot be reproduced by projecting the dynamics onto a single empirical reaction coordinate, a result suggesting the dynamics of this system cannot be correctly described by using a single(More)
Some frequently encountered deficiencies in all-atom molecular simulations, such as nonspecific protein-protein interactions being too strong, and unfolded or disordered states being too collapsed, suggest that proteins are insufficiently well solvated in simulations using current state-of-the-art force fields. To address these issues, we make the simplest(More)
Conventional kinesin is a dimeric motor protein that transports membranous organelles toward the plus-end of microtubules (MTs). Individual kinesin dimers show steadfast directionality and hundreds of consecutive steps, yet the detailed physical mechanism remains unclear. Here we compute free energies for the entire dimer-MT system for all possible(More)