arXiv subjects

Xubiao Peng

Publications and source records attributed to Xubiao Peng.

26 records · Page 2Linked to original sources

arXiv2017

Solution X-ray scattering (S/WAXS) and structure formation in protein dynamics

We propose to develop mean field theory in combination with Glauber algorithm, to model and interpret protein dynamics and structure formation in small to wide angle x-ray scattering (S/WAXS) experiments. We develop the methodology by analysing the Engrailed homeodomain protein as an example. We demonstrate how to interpret S/WAXS data with a good precision and over an extended temperature range. We explain experimentally observed phenomena in terms of protein phase structure, and we make predictions for future experiments how the scattering data behaves at different ambient temperature values. We conclude that a combination of mean field theory with Glauber algorithm has the potential to develop into a highly accurate, computationally effective and predictive tool for analysing S/WAXS data. Finally, we compare our results with those obtained previously in an all-atom molecular dynamics simulation.

q-bio.BM↗

arXiv2016

Thermal unfolding of myoglobin in the Landau-Ginzburg-Wilson approach

The Landau-Ginzburg-Wilson paradigm is applied to model the low-temperature crystallographic C$α$ backbone structure of sperm whale myoglobin. The Glauber protocol is employed to simulate its response to an increase in ambient temperature. The myoglobin is found to unfold from its native state by a succession of $α$-helical intermediates, fully in line with the observed folding and unfolding patterns in denaturation experiments. In particular, a molten globule intermediate is identified with experimentally correct attributes. A detailed, experimentally testable contact map is constructed to characterise the specifics of the unfolding pathway, including the formation of long range interactions. The results reveal how the unfolding process of a protein is driven by the interplay between, and a successive melting of, its modular secondary structure components.

q-bio.BM↗

arXiv2014

Virtual reality based approach to protein heavy-atom structure reconstruction

A commonly recurring problem in structural protein studies, is the determination of all heavy atom positions from the knowledge of the central alpha-carbon coordinates. We employ advances in virtual reality to address the problem. The outcome is a 3D visualisation based technique where all the heavy backbone and side chain atoms are treated on equal footing, in terms of the C-alpha coordinates. Each heavy atom can be visualised on the surfaces of the different two-spheres, that are centered at the other heavy backbone and side chain atoms. In particular, the rotamers are visible as clusters which display strong dependence on the underlying backbone secondary structure. Our method easily detects those atoms in a crystallographic protein structure which have been been likely misplaced. Our approach forms a basis for the development of a new generation, visualisation based side chain construction, validation and refinement tools. The heavy atom positions are identified in a manner which accounts for the secondary structure environment, leading to improved accuracy over existing methods.

q-bio.BM↗

arXiv2014

Aspects of structural landscape of human islet amyloid polypeptide

The human islet amyloid polypeptide (hIAPP) co-operates with insulin to maintain glycemic balance. It also constitutes the amyloid plaques that aggregate in the pancreas of type-II diabetic patients. We have performed extensive in silico investigations to analyse the structural landscape of monomeric hIAPP, which is presumed to be intrinsically disordered. For this we construct from first principles a highly predictive energy function that describes a monomeric hIAPP observed in a NMR experiment, as a local energy minimum. We subject our theoretical model of hIAPP to repeated heating and cooling simulations, back and forth between a high temperature regime where the conformation resembles a random walker and a low temperature limit where no thermal motions prevail. We find that the final low temperature conformations display a high level of degeneracy, in a manner which is fully in line with the presumed intrinsically disordered character of hIAPP. In particular, we identify an isolated family of alpha-helical conformations that might cause the transition to amyloidosis, by nucleation.

q-bio.BM↗

arXiv2014

Peierls-Nabarro Barrier and Protein Loop Propagation

When a self-localized quasiparticle excitation propagates along a discrete one dimensional lattice, it becomes subject to a dissipation that converts the kinetic energy into lattice vibrations. Eventually the kinetic energy does no longer enable the excitation to cross over the minimum energy barrier between neighboring sites, and the excitation becomes localized within a lattice cell. In the case of a protein, the lattice structure consists of the C-alpha backbone. The self-localized quasiparticle excitation is the elemental building block of loops. It can be modeled by a kink which solves a variant of the discrete non-linear Schroedinger equation (DNLS). We study the propagation of such a kink in the case of protein G related albumin-binding domain, using the UNRES coarse-grained molecular dynamics force field. We estimate the height of the energy barriers the kink needs to cross over, in order to propagate along the backbone lattice. We analyse how these barriers gives rise to both stresses and reliefs which control the kink movement. For this, we deform a natively folded protein structure by parallel translating the kink along the backbone away from its native position. We release the transposed kink, and we follow how it propagates along the backbone towards the native location. We observe that the dissipative forces which are exerted on the kink by the various energy barriers, have a pivotal role in determining how a protein folds towards its native state.

cond-mat.soft↗

arXiv2012

On the role of thermal backbone fluctuations in myoglobin ligand gate dynamics

We construct an energy function that describes the crystallographic structure of spermwhale myoglobin backbone. As a model in our construction, we use the Protein Data Bank entry 1ABS that has been measured at liquid helium temperature. Consequently the thermal B-factor fluctuations are very small, which is an advantage in our construction. The energy function that we utilize resembles that of the discrete non-linear Schrodinger equation. Likewise, ours supports solitons as local minimum energy configurations. We describe the 1ABS backbone in terms of solitons with a precision that deviates from 1ABS by an average root-mean-square distance, which is less than the experimentally observed Debye-Waller B-factor fluctuation distance. We then subject the multisoliton solution to extensive numerical heating and cooling experiments, over a very wide range of temperatures. We concentrate in particular to temperatures above 300K and below the theta-point unfolding temperature, which is around 348K. We confirm that the behavior of the multisoliton is fully consistent with Anfinsen's principle, up to very high temperatures. We observe that the structure responds to an increase of temperature consistently in a very similar manner. This enables us to characterize the onset of thermally induced conformational changes in terms of three distinct backbone ligand gates. One of the gates is made of the helix F and the helix E. This is a pathway that is presumed to have a major role in ligand migration between the heme and the exterior. The two other gates are chosen similarly, when open they provide a direct access route for a ligand to reach the heme. We find that out of the three gates we investigate, the one which is formed by helices B and G is the most sensitive one to thermally induced conformational changes. Our approach provides a novel perspective to the important problem of ligand migration.

physics.bio-ph↗

arXiv2011

Soliton concepts and the protein structure

Structural classification shows that the number of different protein folds is surprisingly small. It also appears that proteins are built in a modular fashion, from a relatively small number of components. Here we propose to identify the modular building blocks of proteins with the dark soliton solution of a generalized discrete nonlinear Schrodinger equation. For this we show that practically all protein loops can be obtained simply by scaling the size and by joining together a number of copies of the soliton, one after another. The soliton has only two loop specific parameters and we identify their possible values in Protein Data Bank. We show that with a collection of 200 sets of parameters, each determining a soliton profile that describes a different short loop, we cover over 90% of all proteins with experimental accuracy. We also present two examples that describe how the loop library can be employed both to model and to analyze the structure of folded proteins.

physics.bio-ph↗

arXiv2010

Towards Quantitative Classification of Folded Proteins in Terms of Elementary Functions

A comparative classification scheme provides a good basis for several approaches to understand proteins, including prediction of relations between their structure and biological function. But it remains a challenge to combine a classification scheme that describes a protein starting from its well organized secondary structures and often involves direct human involvement, with an atomary level Physics based approach where a protein is fundamentally nothing more than an ensemble of mutually interacting carbon, hydrogen, oxygen and nitrogen atoms. In order to bridge these two complementary approaches to proteins, conceptually novel tools need to be introduced. Here we explain how the geometrical shape of entire folded proteins can be described analytically in terms of a single explicit elementary function that is familiar from nonlinear physical systems where it is known as the kink-soliton. Our approach enables the conversion of hierarchical structural information into a quantitative form that allows for a folded protein to be characterized in terms of a small number of global parameters that are in principle computable from atomary level considerations. As an example we describe in detail how the native fold of the myoglobin 1M6C emerges from a combination of kink-solitons with a very high atomary level accuracy. We also verify that our approach describes longer loops and loops connecting $α$-helices with $β$-strands, with same overall accuracy.

q-bio.BM↗