Protein–Protein Docking with Large-Scale Backbone Flexibility Using Coarse-Grained Monte-Carlo Simulations

Most of the protein–protein docking methods treat proteins as almost rigid objects. Only the side-chains flexibility is usually taken into account. The few approaches enabling docking with a flexible backbone typically work in two steps, in which the search for protein–protein orientations and structure flexibility are simulated separately. In this work, we propose a new straightforward approach for docking sampling. It consists of a single simulation step during which a protein undergoes large-scale backbone rearrangements, rotations, and translations. Simultaneously, the other protein exhibits small backbone fluctuations. Such extensive sampling was possible using the CABS coarse-grained protein model and Replica Exchange Monte Carlo dynamics at a reasonable computational cost. In our proof-of-concept simulations of 62 protein–protein complexes, we obtained acceptable quality models for a significant number of cases.

Fracture Nucleation Phenomena and Thermally Activated Crack Dynamics in Monocrystals

We explore irreversible thermally activated growth of cracks which are shorter than the Griffith length. Such a growth was anticipated in several studies [Golubović, L. & Feng, S., (1991). Rate of microcrack nucleation, Physical Review A 43, 5223. Golubović, L. & Peredera, A., (1995).  Mechanism of time-delayed fractures, Physical Review E 51, 2799]. We explore this thermally activated growth by means of atomistic Monte-Carlo dynamics simulations of stressed monocrystals. This crack growth is stepwise. Each step is marked by nucleation of a microcavity close to the crack tip, and by creation of a passage connecting the microcavity and the crack. If the external tensile stress is weak, many such nucleation events occur before the crack length reaches the Griffith size. In addition to the simulations, we also present an analytic theory of the stepwise thermally activated crack growth. The theory explains surprising observation form our simulations that the thermally activated crack growth remains fairly well directed in spite of the stochastic nature of the crack growth process.