Mutations in transmembrane (TM) domains of receptor tyrosine kinases are shown to cause a number of inherited diseases and cancer development. Here, we use a combined molecular modeling approach to understand molecular mechanism of effect of G370R and A391E mutations on dimerization of TM domains of human fibroblast growth factor receptor 3 (FGFR3). According to results of Monte-Carlo conformational search in the implicit membrane and further molecular dynamics simulations, TM dimer of this receptor is able to form a number of various conformations, which differ significantly by the free energy of association in a full-atom model bilayer. The aforementioned mutations affect dimerization efficiency of TM segments and lead to repopulation of conformational ensemble for the dimer. Particularly, both mutations do not change the dimerization free energy of the predominant (putative “non-active”) symmetric conformation of TM dimer, while affect dimerization efficiency of its asymmetric (“intermediate”) and alternative symmetric (putative “active”) models. Results of our simulations provide novel atomistic prospective of the role of G370 and A391E mutations in dimerization of TM domains of FGFR3 and their consecutive contributions to the activation pathway of the receptor.
The summary paper argues that the phenomenon of male alliance (friendship) emerges as a consequence of mutual preference demonstrated by male individuals - both human and animal, - and such preference can be empirically captured. Friendly relations between men are built on two different foundations: (1) the principle of biological and social similarity and (2) the principle of psychological complementarity of the alliance members. Friendship is predominantly formed between boys and men of the same ethnic (racial) origin, similar age, behavior, and common social background. By contrast, psychologically friends are selected based on the complementarity of their temperament and main personality traits, such as ergonicity, sthenicity, emotionality, neophobia/neophilia, extraversion/introversion, dependence/independence of behavior, and dominance/submissiveness. These principles trigger the following key effects: a person is more likely to develop an individual preference and find a friend in childhood, and the number of potential friends is very limited.
The aim of this study was to estimate dependence of saccadic latency during stimulation of the dominant and subdominant eye in various conditions of presentation of target and distracting stimuli.
Российские ученые разработали модельный суперкомплекс для долгосрочного прогнозирования развития мировой экономики
A new statistical approach to alignment (finding the longest common subsequence) of two random RNA-type sequences is proposed. We have constructed a generalized ‘dynamic programming’ algorithm for finding the extreme value of the free energy of two noncoding RNAs. In our procedure, we take into account the binding free energy of two random heteropolymer chains which are capable of forming the cloverleaf-like spatial structures typical for RNA molecules. The algorithm is based on two observations: (i) the standard alignment problem can be considered as a zero-temperature limit of a more general statistical problem of binding of two associating heteropolymer chains; (ii) this last problem can be generalized naturally to consider sequences with hierarchical cloverleaf-like structures (i.e. of RNA type). The approach also permits us to perform a ‘secondary structure recovery’. Namely, we can predict the optimal secondary structures of interacting RNAs in a zero-temperature limit knowing only their primary sequences.