Related papers: A Hierarchical Approach to Protein Molecular Evolu…
Protein folding is the intricate process by which a linear sequence of amino acids self-assembles into a unique three-dimensional structure. Protein folding kinetics is the study of pathways and time-dependent mechanisms a protein undergoes…
We have developed a novel Monte Carlo method for simulating the dynamical evolution of stellar systems in arbitrary geometry. The orbits of stars are followed in a smooth potential represented by a basis-set expansion and perturbed after…
The intricate three-dimensional geometries of protein tertiary structures underlie protein function and emerge through a folding process from one-dimensional chains of amino acids. The exact spatial sequence and configuration of amino…
Directed evolution is an iterative laboratory process of designing proteins with improved function by iteratively synthesizing new protein variants and evaluating their desired property with expensive and time-consuming biochemical…
Protein structures are much more conserved than sequences during evolution. Based on this observation, we investigate the consequences of structural conservation on protein evolution. We study seven of the most studied protein folds,…
Identification and alignment of three-dimensional folding of proteins may yield useful information about relationships too remote to be detected by conventional methods, such as sequence comparison, and may potentially lead to prediction of…
Proteins play a key role in facilitating the infectiousness of the 2019 novel coronavirus. A specific spike protein enables this virus to bind to human cells, and a thorough understanding of its 3-dimensional structure is therefore critical…
In this work we propose a physical model of organismal evolution, where phenotype, organism life expectancy, is directly related to genotype i.e. the stability of its proteins which can be determined exactly in the model. Simulating the…
One of the most puzzling and unsolved challenges in molecular biology is understanding how proteins fold. Despite having advanced predictive tools that can accurately estimate the native structures of proteins, we still lack a comprehensive…
Protein folding cooperativity is defined by the nature of the finite-size thermodynamic transition exhibited upon folding: two-state transitions show a free energy barrier between the folded and unfolded ensembles, while downhill folding is…
In this paper we analyze the vibrational spectra of a large ensemble of non-homologous protein structures by means of a novel tool, that we coin the Hierarchical Network Model (HNM). Our coarse-grained scheme accounts for the intrinsic…
Cancer progression and monotonic accumulation models were developed to discover dependencies in the irreversible acquisition of binary traits from cross-sectional data. They have been used in computational oncology and virology but also in…
We introduce a simple "patchy particle" model to study the thermodynamics and dynamics of self-assembly of homomeric protein complexes. Our calculations allow us to rationalize recent results for dihedral complexes. Namely, why evolution of…
Biology stores information and computes at the molecular scale, yet the ways in which it does so are often distinct from human-engineered computers. Mapping biological computation onto architectures familiar to computer science remains an…
Cluster analysis has proved to be an invaluable tool for the exploratory and unsupervised analysis of high dimensional datasets. Among methods for clustering, hierarchical approaches have enjoyed substantial popularity in genomics and other…
For the study of complex synthetic and biological molecular systems by computer simulations one is still restricted to simple model systems or to by far too small time scales. To overcome this problem multiscale techniques are being…
Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the…
Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. Due to their symmetry, these proteins constitute excellent model systems to investigate how evolution relates to structure,…
Protein structures are a very special class among all possible structures. It was suggested that a ``designability principle'' plays a crucial role in nature's selection of protein sequences and structures. Here we provide a theoretical…
An analogy between combinatorial chemistry and Monte Carlo computer simulation is pursued. Examples of how to design libraries for both materials discovery and protein molecular evolution are given. For materials discovery, the concept of…