Related papers: Molecular information theory meets protein folding
It is not merely the position of residues that are of utmost importance in protein function and stability, but the interactions between them. We illustrate, by using a network construction on a set of 595 non-homologous proteins, that…
Assuming that mutation and fixation processes are reversible Markov processes, we prove that the equilibrium ensemble of sequences obeys a Boltzmann distribution with $\exp(4N_e m(1 - 1/(2N)))$, where $m$ is Malthusian fitness and $N_e$ and…
Many enhanced sampling methods, such as Umbrella Sampling, Metadynamics or Variationally Enhanced Sampling, rely on the identification of appropriate collective variables. For proteins, even small ones, finding appropriate collective…
Many native structures of proteins accomodate complex topological motifs such as knots, lassos, and other geometrical entanglements. How proteins can fold quickly even in the presence of such topological obstacles is a debated question in…
We present an analysis of the role of global topology on the structural stability of folded proteins in thermal equilibrium with a heat bath. For a large class of single domain proteins, we compute the harmonic spectrum within the Gaussian…
Computational protein design has a wide variety of applications. Despite its remarkable success, designing a protein for a given structure and function is still a challenging task. On the other hand, the number of solved protein structures…
The protein design problem involves finding polypeptide sequences folding into a given threedimensional structure. Its rigorous algorithmic solution is computationally demanding, involving a nested search in sequence and structure spaces.…
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…
A coarse-grained variational model is used to investigate the polymer dynamics of barrier crossing for a diverse set of two-state folding proteins. The model gives reliable folding rate predictions provided excluded volume terms that induce…
We present a statistical mechanics approach to the protein folding problem. We first review some of the basic properties of proteins, and introduce some physical models to describe their thermodynamics. These models rely on a random…
Information theory provides tools to predict the performance of a learning algorithm on a given dataset. For instance, the accuracy of learning an unknown parameter can be upper bounded by reducing the learning task to hypothesis testing…
Generative machine learning models are increasingly being used to design novel proteins for therapeutic and biotechnological applications. However, the current methods mostly focus on the design of proteins with a fixed backbone structure,…
A transfer-matrix formalism is introduced to evaluate exactly the partition function of the Munoz-Eaton model, relating the folding kinetics of proteins of known structure to their thermodynamics and topology. This technique can be used for…
Protein folding is a central challenge in computational biology, with important applications in molecular biology, drug discovery and catalyst design. As a hard combinatorial optimisation problem, it has been studied as a potential target…
The motion involved in barrier crossing for protein folding are investigated in terms of the chain dynamics of the polymer backbone, completing the microscopic description of protein folding presented in the previous paper. Local reaction…
We refine a protein model that reproduces fundamental aspects of protein thermodynamics. The model exhibits two transitions, hot and cold unfolding. The number of relevant parameters is reduced to three: 1) binding energy of folding…
The three dimensional structure of a protein is an outcome of the interactions of its constituent amino acids in 3D space. Considering the amino acids as nodes and the interactions among them as edges we have constructed and analyzed…
The mechanical unfolding of an engineered protein composed of eight domains of Ig27 is investigated by using atomic force microscopy. Exploiting a fluctuation relation, the equilibrium free energy as a function of the molecule elongation is…
We construct a Hamiltonian for a single domain protein where the contact enthalpy and the chain entropy decrease linearly with the number of native contacts. The hydration effect upon protein unfolding is included by modeling water as ideal…
The biological activity and functional specificity of proteins depend on their native three-dimensional structures determined by inter- and intra-molecular interactions. In this paper, we investigate the geometrical factor of protein…