Related papers: Physical principles underpinning molecular-level p…
Molecular traits, such as gene expression levels or protein binding affinities, are increasingly accessible to quantitative measurement by modern high-throughput techniques. Such traits measure molecular functions and, from an evolutionary…
A full accounting of biological robustness remains elusive; both in terms of the mechanisms by which robustness is achieved and the forces that have caused robustness to grow over evolutionary time. Although its importance to topics such as…
Biases in molecular evolution can significantly influence evolutionary trajectories. They have been described in a variety of contexts such as development and mutation, but not for acquiring new functions (i.e. emergence). Here, we…
We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved…
Proteins are macromolecules that mediate a significant fraction of the cellular processes that underlie life. An important task in bioengineering is designing proteins with specific 3D structures and chemical properties which enable…
A central goal of evolutionary biology is to explain the origins and distribution of diversity across life. Beyond species or genetic diversity, we also observe diversity in the circuits (genetic or otherwise) underlying complex functional…
Enzymes are on the front lines of evolution. All living organisms rely on highly efficient, specific enzymes for growth, sustenance, and reproduction; and many diseases are a consequence of a mutation on an enzyme that affects its catalytic…
Prion and prion-like molecules are a type of self replicating aggregate protein that have been implicated in a variety of neurodegenerative diseases. Over recent decades the molecular dynamics of prions have been characterized both…
Experimental evolution has yielded surprising insights into human history and evolution by shedding light on the roles of chance and contingency in history and evolution, and on the deep evolutionary roots of cooperation, conflict and kin…
A Profile Mixture Model is a model of protein evolution, describing sequence data in which sites are assumed to follow many related substitution processes on a single evolutionary tree. The processes depend in part on different amino acid…
A central biological question is how natural organisms are so evolvable (capable of quickly adapting to new environments). A key driver of evolvability is the widespread modularity of biological networks--their organization as functional,…
We use fitness graphs, or directed cube graphs, for analyzing evolutionary reversibility. The main application is antimicrobial drug resistance. Reversible drug resistance has been observed both clinically and experimentally. If drug…
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…
Deep learning is catalyzing a scientific revolution fueled by big data, accessible toolkits, and powerful computational resources, impacting many fields including protein structural modeling. Protein structural modeling, such as predicting…
One of the main properties of biological systems is modularity, which manifests itself at all levels of their organization, starting with the level of molecular genetics, ending with the level of whole organisms and their communities. In 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…
Computational protein design facilitates discovery of novel proteins with prescribed structure and functionality. Exciting designs were recently reported using novel data-driven methodologies that can be roughly divided into two categories:…
The evolutionary origins of ageing and age-associated diseases continue to pose a fundamental question in biology. This study is concerned with a recently proposed framework, which conceptualises development and ageing as a continuous…
In spite of decades of research, much remains to be discovered about folding: the detailed structure of the initial (unfolded) state, vestigial folding instructions remaining only in the unfolded state, the interaction of the molecule with…
Environmental science almost invariably proposes problems of extreme complexity, typically characterized by strongly nonlinear evolution dynamics. The systems under investigation have many degrees of freedom - which makes them complicated -…