The structure of the double mutant K53,56M has previously been refined at 1.9 A resolution using room-temperature data. The present paper reports the crystal structure of the same mutant K53,56M refined against 1.1 A data collected using synchrotron radiation. A total of 116 main-chain atoms from 29 residues and 44 side chains are modelled in alternate conformations. Most of the interfacial bin...

Motions play a vital role in the functions of many proteins. Discrete conformational transitions to excited states, happening on timescales of hundreds of microseconds, have been extensively characterized. On the other hand, the dynamics of the ground state are widely unexplored. Newly developed high-power relaxation dispersion experiments allow the detection of motions up to a one-digit micros...

Hydrogen peroxide is formed in the cells of plants and animals but is toxic to them. Consequently, living systems have developed mechanisms to rid themselves of hydrogen peroxide, usually by enzyme-catalyzed reduction to water. An understanding of how reactions take place, be they reactions in living systems or reactions in test tubes, begins with a thorough knowledge of the structure of the re...

MOTIVATION Prediction of interactions between protein residues (contact map prediction) can facilitate various aspects of 3D structure modeling. However, the accuracy of ab initio contact prediction is still limited. As structural genomics initiatives move ahead, solved structures of homologous proteins can be used as multiple templates to improve contact prediction of the major conformation of...

Torsional-space Monte Carlo simulations of flexible molecules are usually based on the assumption that all values of dihedral angles have equal probability in the absence of atomic interactions. In the present paper it is shown that this assumption is not valid. Thermodynamic sampling using dihedral angles or other internal coordinates has to account for both the correct metric in conformationa...

Current computational simulation are capable of producing enromous amounts of data. Complete understanding of their features presents a challenge even if very sophisticated visualization techniques are deployed. Computational analysis of conformational behaviour of biologically active compounds represents such simulation. We investigate methods how haptic rendering may contribute to better and ...

We propose an automated protocol for designing the energy landscape of a protein energy function by optimizing its parameters. The parameters are optimized so that not only the global minimum energy conformation becomes native-like, but also the conformations distinct from the native structure have higher energies than those close to the native one. We classify low-energy conformations into thr...

The epidermal growth factor receptor (EGFR) is a key protein in cellular signaling, and its kinase domain (EGFR kinase) is an intensely pursued target of small-molecule drugs. Although both catalytically active and inactive conformations of EGFR kinase have been resolved crystallographically, experimental characterization of the transitions between these conformations remains difficult. Using u...

We propose a multiscale exploration method to characterize the conformational space populated by a protein at equilibrium. The method efficiently obtains a large set of equilibrium conformations in two stages: first exploring the entire space at a coarse-grained level of detail, then narrowing a refined exploration to selected low-energy regions. The coarse-grained exploration periodically adds...

Proteins fluctuate between alternative conformations, which presents a challenge for ligand discovery because such flexibility is difficult to treat computationally owing to problems with conformational sampling and energy weighting. Here we describe a flexible docking method that samples and weights protein conformations using experimentally derived conformations as a guide. The crystallograph...