Biology subjects

Panagiotou, E.

Publications and source records attributed to Panagiotou, E..

3 recordsLinked to original sources

bioRxiv2021

The protein folding rate and the geometry and topology of the native state

Proteins fold in 3-dimensional conformations which are important for their function. Characterizing the global conformation of proteins rigorously and separating secondary structure effects from topological effects is a challenge. New developments in Applied Knot Theory allow to characterize the topological characteristics of proteins (knotted or not). By analyzing a small set of two-state and multi-state proteins with no knots or slipknots, our results show that 95.4% of the analyzed proteins have non-trivial topological characteristics, as reflected by the second Vassiliev measure, and that the logarithm of the experimental protein folding rate depends on both the local geometry and the topology of the proteins native state.

bioinformatics↗

bioRxiv2021

The local topological free energy of the SARS-CoV-2 Spike protein

The novel coronavirus SARS-CoV-2 infects human cells using a mechanism that involves binding and structural rearrangement of its spike protein. Understanding protein rearrangement and identifying specific residues where mutations affect protein rearrangement has attracted a lot of attention for drug development. We use a mathematical method introduced in [9] to associate a local topological/geometrical free energy along the SARS-CoV-2 spike protein backbone. Our results show that the total local topological free energy of the SARS-CoV-2 spike protein monotonically decreases from pre-to post-fusion and that its distribution along the protein domains is related to their activity in protein rearrangement. By using density functional theory (DFT) calculations with inclusion of solvent effects, we show that high local topological free energy conformations are unstable compared to those of low topological free energy. By comparing to experimental data, we find that the high local topological free energy conformations in the spike protein are associated with mutations which have the largest experimentally observed effect to protein rearrangement.

bioinformatics↗

bioRxiv2021

The topological free energy of proteins

Protein folding, the process by which proteins attain a 3-dimensional conformation necessary for their function, remains an important unsolved problem in biology. A major gap in our understanding is how local properties of proteins relate to their global properties. In this manuscript, we use the Writhe and Torsion to introduce a new local topological/geometrical free energy that can be associated to 4 consecutive residues along protein backbone. By analyzing a culled protein dataset from the PDB, our results show that high local topological free energy conformations are independent of sequence and may be involved in the rate limiting step in protein folding. By analyzing a set of 2-state single domain proteins, we find that the total local topological free energy of these proteins correlates with the experimentally observed folding rates reported in [29].

bioinformatics↗