Related papers: A topological perspective into the sequence and co…
Much scientific enquiry across disciplines is founded upon a mechanistic treatment of dynamic systems that ties form to function. A highly visible instance of this is in molecular biology, where an important goal is to determine…
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…
Designing novel proteins with desired functions is crucial in biology and chemistry. However, most existing work focus on protein sequence design, leaving protein sequence and structure co-design underexplored. In this paper, we propose…
The number of protein structures is far less than the number of sequences. By imposing simple generic features of proteins (low energy and compaction) on all possible sequences we show that the structure space is sparse compared to the…
Accurately modeling and designing protein complex structures is a central problem in computational structural biology, with broad implications for understanding cellular function and developing therapeutics. This thesis investigates two…
Computational protein design aims at constructing novel or improved functions on the structure of a given protein backbone and has important applications in the pharmaceutical and biotechnical industry. The underlying combinatorial…
Predicting the binding free energy between antibodies and antigens is a key challenge in structure-aware biomolecular modeling, with direct implications for antibody design. Most existing methods either rely solely on sequence embeddings or…
The spectrum and scale of fluctuations in protein structures affect the range of cell phenomena, including stability of protein structures or their fragments, allosteric transitions and energy transfer. The study presents a…
Flexibility governs the many properties of materials and is crucial for the function of proteins and biopolymers. However, how the self-assembly of flexibly bonded particles can lead to larger structures with global reconfigurability is…
The choice of structural resolution is a fundamental aspect of protein modelling, determining the balance between descriptive power and interpretability. Although atomistic simulations provide maximal detail, much of this information is…
The structure and function of a protein are determined by its amino acid sequence. While random mutations change a protein's sequence, evolutionary forces shape its structural fold and biological activity. Studies have shown that neutral…
In this study, we propose an analytic statistical mechanics approach to solve a fundamental problem in biological physics called protein design. Protein design is an inverse problem of protein structure prediction, and its solution is the…
Is protein secondary structure primarily determined by local interactions between residues closely spaced along the amino acid backbone, or by non-local tertiary interactions? To answer this question we have measured the entropy densities…
Computational protein design has the potential to deliver novel molecular structures, binders, and catalysts for myriad applications. Recent neural graph-based models that use backbone coordinate-derived features show exceptional…
Proteins are the major building blocks of life, and actuators of almost all chemical and biophysical events in living organisms. Their native structures in turn enable their biological functions which have a fundamental role in drug design.…
Correlation patterns in multiple sequence alignments of homologous proteins can be exploited to infer information on the three-dimensional structure of their members. The typical pipeline to address this task, which we in this paper refer…
The hydrophobic effect stabilizes the native structure of proteins by minimizing the unfavourable interactions between hydrophobic residues and water through the formation of a hydrophobic core. Here we include the entropic and enthalpic…
The flawless functioning of a protein is essentially linked to its own three-dimensional structure. Therefore, the prediction of a protein structure from its amino acid sequence is a fundamental problem in many fields that draws researchers…
The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…
The notion of energy landscapes provides conceptual tools for understanding the complexities of protein folding and function. Energy Landscape Theory indicates that it is much easier to find sequences that satisfy the "Principle of Minimal…