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In this paper we propose a novel theoretical framework for interpreting long-range dynamical correlations unveiled in proteins through NMR measurements. The theoretical rationale relies on the hypothesis that correlated motions in proteins…
A central challenge in the study of protein evolution is the identification of historic amino acid sequence changes responsible for creating novel functions observed in present-day proteins. To address this problem, we developed a new…
Understanding the link between structure and function in proteins is fundamental in molecular biology and proteomics. A central question in this context is whether allostery - where the binding of a molecule at one site affects the activity…
Cellular behavior is governed by gene regulatory processes that are intrinsically dynamic and nonlinear, and are subject to non-negligible amounts of random fluctuations. Such conditions are ubiquitous in physical systems, where they have…
Relevance of mode coupling to energy/information transfer during protein function, particularly in the context of allosteric interactions is widely accepted. However, existing evidence in favor of this hypothesis comes essentially from…
Allosteric regulation is often viewed as thermodynamic in nature. However protein internal motions during an enzymatic reaction cycle can be slow hopping processes over numerous potential barriers. We propose that regulating molecules may…
Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a…
Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored.…
Recent advances in protein function prediction exploit graph-based deep learning approaches to correlate the structural and topological features of proteins with their molecular functions. However, proteins in vivo are not static but…
On the microscopic level, biological signal transmission relies on coordinated structural changes in allosteric proteins that involve sensor and effector modules. The timescales and microscopic details of signal transmission in proteins are…
Evolution is simultaneously driven by a number of processes such as mutation, competition and random sampling. Understanding which of these processes is dominating the collective evolutionary dynamics in dependence on system properties is a…
Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…
Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. While high-throughput methods have produced large numbers of sequence-function pairs, functional assays do not distinguish…
Neurotensin receptor 1 (NTSR1), a member of the Class A G protein-coupled receptor superfamily, plays an important role in modulating dopaminergic neuronal activity and eliciting opioid-independent analgesia. Recent studies suggest that…
The functions of most genetic circuits require sufficient degrees of cooperativity in the circuit components. While mechanisms of cooperativity have been studied most extensively in the context of transcriptional initiation control,…
The function of proteins arises from cooperative interactions and rearrangements of their amino acids, which exhibit large-scale dynamical modes. Long-range correlations have also been revealed in protein sequences, and this has motivated…
Natural protein sequences somehow encode the structural forms that these molecules adopt. Recent developments in structure-prediction are agnostic to the mechanisms by which proteins fold and represent them as static objects. However, the…
Along with recent progress in structural biology and genome biology, structural dynamics of molecular systems including nucleic acids has attracted attention in the context of gene regulation. Structure-function relationship is an important…
Current all-atom potential based molecular dynamics (MD) allow the identification of a protein's functional motions on a wide-range of time-scales, up to few tens of ns. However, functional large scale motions of proteins may occur on a…
Non-coding RNAs are ubiquitous, but the discovery of new RNA gene sequences far outpaces research on their structure and functional interactions. We mine the evolutionary sequence record to derive precise information about function and…