Related papers: Factors controlling protein evolvability, at the m…
We develop a path-based approach to continuous-time random walks on networks with arbitrarily weighted edges. We describe an efficient numerical algorithm for calculating statistical properties of the stochastic path ensemble. After…
In general, cellular phenotypes, as measured by concentrations of cellular components, involve large degrees of freedom. However, recent measurement has demonstrated that phenotypic changes resulting from adaptation and evolution in…
For the vast majority of naturally occurring, small, single domain proteins folding is often described as a two-state process that lacks detectable intermediates. This observation has often been rationalized on the basis of a nucleation…
Textual analysis of typical microbial genomes reveals that they have the statistical characteristics of a DNA sequence of a much shorter length. This peculiar property supports an evolutionary model in which a genome evolves by random…
The understanding, and even the description of protein folding is impeded by the complexity of the process. Much of this complexity can be described and understood by taking a statistical approach to the energetics of protein conformation,…
The dynamical characterization of proteins is crucial to understand protein function. From a microscopic point of view, protein dynamics is governed by the local atomic interactions that, in turn, trigger the functional conformational…
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…
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…
Predicting protein properties is paramount for biological and medical advancements. Current protein engineering mutates on a typical protein, called the wild-type, to construct a family of homologous proteins and study their properties.…
Naturally evolving proteins gradually accumulate mutations while continuing to fold to thermodynamically stable native structures. This process of neutral protein evolution is an important mode of genetic change, and forms the basis for the…
Cells often exhibit different and stable phenotypes from the same DNA sequence. Robustness and plasticity of such cellular states are controlled by diverse transcriptional and epigenetic mechanisms, among them the modification of…
Proteins are intricate molecular machines whose complexity arises from the heterogeneity of the amino acid building blocks and their dynamic network of many-body interactions. These nanomachines gain function when put in the context of a…
Natural protein sequences that self-assemble to form globular structures are compact with high packing densities in the folded states. It is known that proteins unfold upon addition of denaturants, adopting random coil structures. The…
Identifying and characterizing mutational paths is an important issue in evolutionary biology and in bioengineering. We here introduce a generic description of mutational paths in terms of the goodness of sequences and of the mutational…
Biological forces govern essential cellular and molecular processes in all living organisms. Many cellular forces, e.g. those generated in cyclic conformational changes of biological machines, have repetitive components. However, little is…
Under constant selection, each trait has a fixed fitness, and small mutation rates allow populations to efficiently exploit the optimal trait. Therefore it is reasonable to expect mutation rates will evolve downwards. However, we find this…
How do protein structure prediction models fold proteins? We investigate this question by tracing how ESMFold folds a beta hairpin, a prevalent structural motif. Through counterfactual interventions on model latents, we identify two…
Understanding of the evolutionary origins of protein structures represents a key component of the understanding of molecular evolution as a whole. Here we seek to elucidate how the features of an underlying protein structural "space" might…
Complex systems, such as life and languages, are governed by principles of evolution. The analogy and comparison between biology and linguistics\cite{alphafold2, RoseTTAFold, lang_virus, cell language, faculty1, language of gene, Protein…
This paper demonstrates that simple yet important characteristics of coevolution can occur in evolutionary algorithms when only a few conditions are met. We find that interaction-based fitness measurements such as fitness (linear) ranking…