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Jiapu Zhang

Publications and source records attributed to Jiapu Zhang.

At least 19 recordsLinked to original sources
arXiv2024

Molecular dynamics and optimization studies of horse prion protein wild type and its S167D mutant

Prion diseases or called transmissible spongiform encephalopathies are fatal neurodegenerative diseases characterised by the accumulation of an abnormal prion protein isoform (rich in beta-sheets - about 30% alpha-helix and 43% beta-sheet), which is converted from the normal prion protein (predominant in alpha-helix - about 42% alpha-helix and 3% beta-sheet). However, prion disease has not been reported in horses up to now; therefore, horses are known to be a species resistant to prion diseases. Residue S167 in horse has been cited as critical protective residue for encoding prion protein conformational stability in prion-resistance. According to the protein-only hypothesis, abnormal prion protein is responsible for both spongiform degeneration of the brain and disease transmissibility. Thus, understanding the conformational dynamics of abnormal prion protein from normal prion protein is a key to developing effective therapies. This article is to do molecular dynamics and optimization studies on the horse normal prion protein wild-type and its S167D mutant respectively to understand their conformational dynamics and optimized confirmation; interesting results will be discussed.

physics.bio-ph↗
arXiv2020

Molecular Dynamics Studies of the Bufallo Prion Protein Structured Region at Higher Temperatures

Molecular dynamics (MD) studies of buffalo prion protein (BufPrP$^\text{C}$) [Zhang JP et al.(2016) J Biomol Struct Dyn 34(4):762-777] showed that the structure of this protein is very stable at room temperature (whether under neutral pH or low pH environments). In order to understand the reason why buffalo is lowly susceptible to prion diseases and why BufPrP$^\text{C}$ is so stable at room temperature, this paper will prolong our MD running time at room temperature and extend our research to higher temperatures to study this BufPrP$^\text{C}$ structure furthermore. From the salt bridge point of view we found an important reason why BufPrP$^\text{C}$ is so stable at room temperature and this might be a nice clue of drug discovery or drug design for the treatment of prion diseases.

physics.bio-ph↗
arXiv2020

Molecular Dynamics Studies of Dog Prion Protein Wild-type and Its D159N Mutant

Prion diseases (e.g. "mad cow" disease in cattle, chronic wasting disease in deer and elk, CJD in humans) have been a major public health concern affecting humans and almost all animals. However, dogs are strongly resistant to prion diseases. Recently, it was reported that the single (surface) residue D159 is sufficient to confer protection against protein conformational change and pathogenesis, providing conformational stability for dog prion protein (Neurobiology of Disease Volume 95 (November 2016) pages 204-209). This paper studies dog prion protein wild-type and D159N mutant through molecular dynamics techniques. Molecular dynamics results reveal sufficient structural informatics on the residue at position 159 to understand the mechanism underlying the resistance to prion diseases of dogs.

physics.bio-ph↗
arXiv2019

The polar clasps of a bank vole PrP(168--176) prion protofibril revisiting

On 2018-01-17 two electron crystallography structures (with PDB entries 6AXZ, 6BTK) on a prion protofibril of bank vole PrP(168-176) (a segment in the PrP $β$2-$α$2 loop) were released into the PDB Bank. The paper published by [Nat Struct Mol Biol 25(2):131-134 (2018)] reports some polar clasps for these two crystal structures, and "an intersheet hydrogen bond between Tyr169 and the backbone carbonyl of Asn171 on an opposing strand." - this hydrogen bond is not between the neighbouring Chain B and Chain A directly. In addition, by revisiting the polar clasps, we found another two hydrogen bonds (B.Asn171@H-A.Gln172@OE1, B.Tyr169@OH-A.Gln172@N) between the strand A of one sheet and the opposing strand B of the mating sheet. For the neighbouring two single $β$-sheets AB, the two new hydrogen bonds are completely different from the experimental one (an intersheet hydrogen bond between Tyr169 and the backbone carbonyl of Asn171 on an opposing strand) in [Nat Struct Mol Biol 25(2):131-134 (2018)].

physics.bio-ph↗
arXiv2015

The Hybrid Idea of Optimization Methods Applied to the Energy Minimization of (Prion) Protein Structures Focusing on the beta2-alpha2 Loop

In molecular mechanics, current generation potential energy functions provide a reasonably good compromise between accuracy and effectiveness. This paper firstly reviewed several most commonly used classical potential energy functions and their optimization methods used for energy minimization. To minimize a potential energy function, about 95\% efforts are spent on the Lennard-Jones potential of van der Waals interactions; we also give a detailed review on some effective computational optimization methods in the Cambridge Cluster Database to solve the problem of Lennard-Jones clusters. From the reviews, we found the hybrid idea of optimization methods is effective, necessary and efficient for solving the potential energy minimization problem and the Lennard-Jones clusters problem. An application to prion protein structures is then done by the hybrid idea. We focus on the $β$2-$α$2 loop of prion protein structures, and we found (i) the species that has the clearly and highly ordered $β$2-$α$2 loop usually owns a 3$_{10}$-helix in this loop, (ii) a "$π$-circle" Y128--F175--Y218--Y163--F175--Y169--R164--Y128(--Y162) is around the $β$2-$α$2 loop.

math.OC↗
arXiv2015

Molecular Dynamics Studies on the Buffalo Prion Protein

It was reported that buffalo is a low susceptibility species resisting to prion diseases, which are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of species. In molecular structures, TSE neurodegenerative diseases are caused by the conversion from a soluble normal cellular prion protein, predominantly with alpha-helices, into insoluble abnormally folded infectious prions, rich in beta-sheets. This paper studies the molecular structure and structural dynamics of buffalo prion protein, in order to reveal the reason why buffalo are resistant to prion diseases. We first did molecular modeling of a homology structure constructed by one mutation at residue 143 from the Nuclear Magnetic Resonance structure of bovine and cattle PrP(124-227); immediately we found for buffalo PrPC(124-227) there are 5 hydrogen bonds at Asn143, but at this position bovine/cattle do not have such hydrogen bonds. Same as that of rabbits, dogs or horses, our molecular dynamics studies also confirmed there is a strong salt bridge ASP178-ARG164 (O-N) keeping the beta2-alpha2 loop linked in buffalo. We also found there is a very strong hydrogen bond SER170-TYR218 linking this loop with the C-terminal end of alpha-helix H3. Other information such as (i) there is a very strong salt bridge HIS187-ARG156 (N-O) linking alpha-helices H2 and H1 (if mutation H187R is made at position 187 then the hydrophobic core of PrPC will be exposed), (ii) at D178, there is a hydrogen bond Y169-D178 and a polar contact R164-D178 for BufPrPC instead of a polar contact Q168-D178 for bovine PrPC, (iii) BufPrPC owns 3-10 helices at 125-127, 152-156 and in the beta2-alpha2 loop respectively, and (iv) in beta2-alpha2 loop there are strong pi-contacts, etc, has been discovered.

physics.bio-ph↗
arXiv2015

A Review on the Salt Bridge Between ASP177 and ARG163 of Wild-Type Rabbit Prion Protein

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep and goats, cattle, deer, elks, humans and mice etc., but rabbits have a low susceptibility to be infected by prion diseases with respect to other species. The stability of rabbit prion protein is due to its highly ordered β2-α2 loop (PLoS One 5(10) e13273 (2010); Journal of Biological Chemistry 285(41) 31682-31693 (2010)) and a hydrophobic staple helix-capping motif (PNAS 107(46) 19808-19813 (2010); PLoS One 8 (5) e63047 (2013)). The β2-α2 loop and the tail of Helix 3 it interacts with have been a focus in prion protein structure studies. For this loop we found a salt bridge linkage ASP177-ARG163 (O-N) (Journal of Theoretical Biology 342 (7 February 2014) 70-82 (2014)). Some scientists said on the 2FJ3.pdb NMR file of the rabbit prion protein, the distance of ASP177-ARG163 (O-N) gives the salt bridge of about 10 Å which is nearly null in terms of energy and such a salt bridge is not observed in their work. But, from the 3O79.pdb X-ray file of the rabbit prion protein, we can clearly observe this salt bridge. This article analyses the NMR and X-ray structures and gives an answer to the above question: the salt bridge presents at pH 6.5 in the X-ray structure is simply gone at pH 4.5 in the NMR structure is simply due to the different pH values that impact electrostatics at the salt bridge and hence also impact the structures. Moreover, some molecular dynamics simulation results of the X-ray structure are reported in this article to reveal the secrets of the structural stability of rabbit prion protein.

physics.bio-ph↗
arXiv2014

A survey and a molecular dynamics study on the (central) hydrophobic region of prion proteins

Prion diseases are invariably fatal neurodegenerative diseases that affect humans and animals. Unlike most other amyloid forming neurodegenerative diseases, these can be highly infectious. Prion diseases occur in a variety of species. They include the fatal human neurodegenerative diseases Creutzfeldt-Jakob Disease (CJD), Fatal Familial Insomnia (FFI), Gerstmann-Straussler-Scheinker syndrome (GSS), Kuru, the bovine spongiform encephalopathy (BSE or 'mad-cow' disease) in cattle, the chronic wasting disease (CWD) in deer and elk, and scrapie in sheep and goats, etc. Transmission across the species barrier to humans, especially in the case of BSE in Europe, CWD in North America, and variant CJDs (vCJDs) in young people of UK, is a major public health concern. Fortunately, scientists reported that the (central) hydrophobic region of prion proteins (PrP) controls the formation of diseased prions. This article gives a detailed survey on PrP hydrophobic region and does molecular dynamics studies of human PrP(110-136) to confirm some findings from the survey. The structural bioinformatics presented in this article can be helpful as a reference in three-dimensional images for laboratory experimental works to study PrP hydrophobic region.

physics.bio-ph↗
arXiv2014

Molecular dynamics studies on the NMR structures of rabbit prion protein wild-type and mutants: surface electrostatic charge distributions

Prion is a misfolded protein found in mammals that causes infectious diseases of the nervous system in humans and animals. Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep and goats, cattle, deer, elk and humans etc. Recent studies have shown that rabbits have a low susceptibility to be infected by prion diseases with respect to other animals including humans. The present study employs molecular dynamics (MD) means to unravel the mechanism of rabbit prion proteins (RaPrPC) based on the recently available rabbit NMR structures (of the wild-type and its two mutants of two surface residues). The electrostatic charge distributions on the protein surface are the focus when analysing the MD trajectories. It is found that we can conclude that surface electrostatic charge distributions indeed contribute to the structural stability of wild-type RaPrPC; this may be useful for the medicinal treatment of prion diseases.

physics.bio-ph↗
arXiv2013

A global and superlinearly convergent algorithm for nonlinear nondifferential convex programming problems with a generalized Armijo line-search

This paper presents a new generalized Armijo's line-search method, and combines it with a phi-regulation defined to obtain a new algorithm solving the very general non-linear non-smooth convex programming. For the algorithm designed, the global convergence is proved and the algorithm has super-linear convergent rate under very weak conditions. This paper generalized the results of reference "Fukushima M and Qi LQ (1996) SIAM Journal of Optimization 6: 1106-20".

math.OC↗
arXiv2013

Simulated annealing: in mathematical global optimization computation, hybrid with local or global search, and practical applications in crystallography and molecular modelling

Simulated annealing (SA) was inspired from annealing in metallurgy, a technique involving heating and controlled cooling of a material to increase the size of its crystals and reduce their defects, both are attributes of the material that depend on its thermodynamic free energy. In this Paper, firstly we will study SA in details on its practical implementation. Then, hybrid pure SA with local (or global) search optimization methods allows us to be able to design several effective and efficient global search optimization methods. In order to keep the original sense of SA, we clarify our understandings of SA in crystallography and molecular modeling field through the studies of prion amyloid fibrils.

math.OC↗
arXiv2013

Molecular dynamics studies on the NMR and X-ray structures of rabbit prion protein wild-type and mutants

Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep, goats, mice, humans, chimpanzees, hamsters, cattle, elks, deer, minks, cats, chicken, pigs, turtles, etc. These neurodegenerative diseases are caused by the conversion from a soluble normal cellular protein into insoluble abnormally folded infectious prions and the conversion is believed to involve conformational change from a predominantly alpha-helical protein to one rich in beta-sheet structure. Such conformational changes may be amenable to study by molecular dynamics (MD) techniques. For rabbits, classical studies show they have a low susceptibility to be infected, but in 2012 it was reported that rabbit prion can be generated (though not directly) and the rabbit prion is infectious and transmissible (Proceedings of the National Academy of Sciences USA 109(13): 5080-5). This paper studies the NMR and X-ray molecular structures of rabbit prion protein wild-type and mutants by MD techniques, in order to understand the specific mechanism of rabbit prion protein and rabbit prions.

q-bio.BM↗
arXiv2013

The Methicillin-Resistant Staphylococcus Aureus Infection Controls

Multi-resistant organisms (MROs), the bacteria that are resistant to a number of different antibiotics, have been very popular around the world in recent years. They are very difficult to treat but highly infectious in humans. MRSA (Methicillin-Resistant Staphylococcus Aureus) is one of the MROs. It is believed that in 2007 more people died of MRSA than of AIDS worldwide. In Australia "there are about 2000 people per year who have a bloodstream infection with the MRSA germ and the vast majority of those get them from health care procedure" (Nader, 2005). It is acknowledged as a significant challenge to Australian hospitals for MRSA infection control. Nursing professionals are in urgent need of the study of MRSA nosocomial infection controls. This review provides insight into the hand washing and isolation infection-control strategies for MRSA. The important technologies on those two aspects worldwide are well surveyed, compared, contrasted, and discussed. The review is to do a complete survey on the hand washing and isolation technologies of infection controls for MRSA and try to provide some possible recommendations for Australian hospitals.

q-bio.OT↗
arXiv2013

Molecular Dynamics Studies on 3D Structures of the Hydrophobic Region PrP(109-136)

Prion diseases caused by the conversion from a soluble normal cellular prion protein into insoluble abnormally folded infectious prions, are invariably fatal and highly infectious degenerative diseases that affect a wide variety of mammalian species. The palindrome and the Glycine-rich conserved segment in the hydrophobic region 109-136 control the conversion from normal prion protein to form into diseased prions. This paper gives detailed reviews on the 109-136 region and presents the studies of its 3D structures and structural dynamics.

q-bio.BM↗
arXiv2012

Canonical dual theory applied to a Lennard-Jones potential minimization problem

The simplified Lennard-Jones (LJ) potential minimization problem is $f(x)=4\sum_{i=1}^N \sum_{j=1,j<i}^N (\frac{1}{τ_{ij}^6} -\frac{1}{τ_{ij}^3}) {subject to} x\in \mathbb{R}^n,$ where $τ_{ij}=(x_{3i-2}-x_{3j-2})^2 +(x_{3i-1}-x_{3j-1})^2 +(x_{3i} -x_{3j})^2$, $(x_{3i-2},x_{3i-1},x_{3i})$ is the coordinates of atom $i$ in $\mathbb{R}^3$, $i,j=1,2,...,N(\geq 2 \quad \text{integer})$, $n=3N$ and $N$ is the whole number of atoms. The nonconvexity of the objective function and the huge number of local minima, which is growing exponentially with $N$, interest many mathematical optimization experts. In this paper, the canonical dual theory elegantly tackles this problem illuminated by the amyloid fibril molecular model building. Keywords: Mathematical Canonical Duality Theory $\cdot$ Mathematical Optimization $\cdot$ Lennard-Jones Potential Minimization Problem $\cdot$ Global Optimization.

math.OC↗
arXiv2012

The LBFGS Quasi-Newtonian Method for Molecular Modeling Prion AGAAAAGA Amyloid Fibrils

Experimental X-ray crystallography, NMR (Nuclear Magnetic Resonance) spectroscopy, dual polarization interferometry, etc are indeed very powerful tools to determine the 3-Dimensional structure of a protein (including the membrane protein); theoretical mathematical and physical computational approaches can also allow us to obtain a description of the protein 3D structure at a submicroscopic level for some unstable, noncrystalline and insoluble proteins. X-ray crystallography finds the X-ray final structure of a protein, which usually need refinements using theoretical protocols in order to produce a better structure. This means theoretical methods are also important in determinations of protein structures. Optimization is always needed in the computer-aided drug design, structure-based drug design, molecular dynamics, and quantum and molecular mechanics. This paper introduces some optimization algorithms used in these research fields and presents a new theoretical computational method - an improved LBFGS Quasi-Newtonian mathematical optimization method - to produce 3D structures of Prion AGAAAAGA amyloid fibrils (which are unstable, noncrystalline and insoluble), from the potential energy minimization point of view. Because the NMR or X-ray structure of the hydrophobic region AGAAAAGA of prion proteins has not yet been determined, the model constructed by this paper can be used as a reference for experimental studies on this region, and may be useful in furthering the goals of medicinal chemistry in this field.

math.OC↗
arXiv2012

Computational Potential Energy Minimization Studies on the Prion AGAAAAGA Amyloid Fibril Molecular Structures

X-ray crystallography, NMR (Nuclear Magnetic Resonance) spectroscopy, and dual polarization interferometry, etc are indeed very powerful tools to determine the 3D structures of proteins (including the membrane proteins), though they are time-consuming and costly. However, for some proteins, due to their unstable, noncrystalline and insoluble nature, these tools cannot work. Under this condition, mathematical and physical theoretical methods and computational approaches allow us to obtain a description of the protein 3D structure at a submicroscopic level. This Chapter presents some practical and useful mathematical optimization computational approaches to produce 3D structures of the Prion AGAAAAGA Amyloid Fibrils, from a potential energy minimization point of view. X-ray crystallography finds the X-ray final structure of a protein, which usually need refinements in order to produce a better structure. The computational methods presented in this Chapter can be also acted as a tool for the refinements.

math.OC↗