Short Polypeptide Chains Research Articles

Processing helix–coil transition data: Account of chain length and solvent effects

Numerous nanobiotechnologies include manipulations of short polypeptide chains. The conformational properties of these polypeptides are studied in vitro by circular dichroism and time-resolved infrared spectroscopy. To find out the interaction parameters, the measured temperature dependence of normalized helicity degree needs to be further processed by fitting to a model. Using recent advances in the Hamiltonian formulation of the classical Zimm and Bragg model, we explicitly include chain length and solvent effects in the theoretical description. The expression for the helicity degree we suggest successfully fits the experimental data and provides hydrogen bonding energies and nucleation parameter values within the standards in the field.

Engineering an Fc-Fusion of a Capsule Degrading Enzyme for the Treatment of Anthrax.

Polymers of d-glutamic acid (PDGA) form the capsule of the highly virulent Ames strain of B.anthracis. PDGA is antiphagocytic and weakly immunogenic; it enables the bacteria to evade the innate immune responses. CapD is an enzyme that catalyzes the covalent anchoring of PDGA. CapD is an Ntn-amido hydrolase that utilizes an internal Thr-352 as its nucleophile and general acid and base. An internal cleavage produces a free N-terminal Thr-352 and a short and long polypeptide chain. The chains were circularly permuted (CP) to move Thr-352 to the N-terminus of the polypeptide. We previously showed that a branched PEG-CapDS334C-CP could protect mice (80% survival) against a 5 LD50 challenge with B.anthracis Ames without the use of antibiotics, monoclonals, or vaccines. In attempts to improve the in vivo circulation time of CapD and enhance its avidity to its polymeric substrate, an Fc-domain of a mouse IgG1 was fused to CapDS334C-CP and the linker length and sequence were optimized. The resulting construct, Fc-CapDS334C-CP, then was pegylated with a linear 2 kDa mPEG at S334C to produce mPEG-Fc-CapDS334C-CP. Interestingly, the fusion of the Fc-domain and incorporation of the S334C mutation imparted acid stability, but slightly reduced the kcat (∼ 2-fold lower). In vivo, the measured protein concentration in sera was higher for the Fc-fusion constructs compared to the mPEG-Fc-CapDS334C-CP. However, the exposure calculated from measured sera enzymatic activity was higher for the mPEG-CapDS334C-CP. The pegylated Fc-fusion was less active than the PEG-CapDS334C-CP, but detectable in sera at 24 h by immunoblot. Here we describe the engineering of a soluble, active, pegylated Fc-fusion of B.anthracis CapD (mPEG-Fc-CapD-CP) with activity in vitro, in serum, and on encapsulated bacteria.

Studying folding leftrightarrow unfolding dynamics of solvated alanine polypeptides using molecular dynamics

The atomistic description of the folding process of a structureless chain of amino acids to a functioning protein is still considered to be a challenge for computational biophysics. An in-depth understanding of protein-folding can be achieved through atomistic dynamics accounting for the solvent effects, combined with the theoretical description of conformational changes in shorter polypeptide chains. The present paper studies the folding transitions in short polypeptide chains consisting of 11 alanine residues in explicit solvent employing all-atom molecular dynamics. The multiple observed folding leftrightarrow unfolding events of the peptide are interpreted as a dynamic process and rationalised through the analysis of the potential energy surface of the system. It is demonstrated that alanine polypeptide folding dynamics is governed by the backbone dihedral angles and involves the formation of spontaneously folded alpha -helices which emerge and live for ca. 1–20 picoseconds. The helical content within the polypeptide at different temperatures was quantified through a statistical mechanics approach, which showed a reasonable agreement with the results of molecular dynamics simulations and experiments performed for alanine-rich peptides.Graphical abstract

Computational Study on Pazopanib and Pemetrexed Anticancer Drug Molecules Interacting with a Small Peptide Link

Cancer is a group of diseases that are defined as uncontrolled cell proliferation, impaired function of vital tissues and cell death. Chemotherapy is treatment using anti-cancer drugs to destroy cancer cells or control the growth of these cells. In chemotherapy applications pharmacologically active anticancer drugs reach with low specificity to tumor tissue, and also their toxicity is dose-dependent. Classical drug administration routes are either oral or intravenous. Orally taken pills result in irregular pharmacokinetics due to the passages of different metabolic pathways and their low specificity. This leads to frequent damage to healthy tissues. Nanoparticle containing drug delivery systems may overcome these harmful side effects partially (or sometimes totally). Binding peptide-drug conjugates inside of some appropriate nanoparticles is one of the prominent methods among targeted drug delivery systems. Such a system containing Pazopanib (Pz) and Pemetrexed (Pm) drug complexes attached to magnetite nanoparticles with a short polypeptide chain (Ala-Lys-Ala-Leu-Arg-Cys) were designed in our laboratory. In the present study, we computationally investigate the conjugation mechanisms of Pz and Pm drug molecules to the above-mentioned polypeptide chain. The stable structures on the complex formation pathways and their free energy values were obtained at the B3LYP/6-31G(d) level in the water. The mechanism of Pept-Pz complex formation has two steps whose free energy barriers are found to be 21.37 and 27.72 kcal/mol. On the other hand, the free energy barrier of the Pept-Pm complex having a single-step mechanism was calculated as 28.16 kcal/mol.

Introducing Pep McConst-A user-friendly peptide modeler for biophysical applications.

We are introducing Pep McConst-a software that employs a Monte-Carlo algorithm to construct 3D structures of polypeptide chains which could subsequently be studied as stand-alone macromolecules or complement the structure of known proteins. Using an approach to avoid steric clashes, Pep McConst allows to create multiple structures for a predefined primary sequence of amino acids. These structures could then effectively be used for further structural analysis and investigations. The article introduces the algorithm and describes its user-friendly approach that was made possible through the VIKING online platform. Finally, the manuscript provides several highlight examples where Pep McConst was used to predict the structure of the C-terminal of a known protein, generate a missing bit of already crystallized protein structures and simply generate short polypeptide chains.

Propagation of Fibrillar Structural Forms in Proteins Stopped by Naturally Occurring Short Polypeptide Chain Fragments.

Amyloids characterized by unbounded growth of fibrillar structures cause many pathological processes. Such unbounded propagation is due to the presence of a propagating hydrophobicity field around the fibril’s main axis, preventing its closure (unlike in globular proteins). Interestingly, similar fragments, commonly referred to as solenoids, are present in many naturally occurring proteins, where their propagation is arrested by suitably located “stopper” fragments. In this work, we analyze the distribution of hydrophobicity in solenoids and in their corresponding “stoppers” from the point of view of the fuzzy oil drop model (called FOD in this paper). This model characterizes the unique linear propagation of local hydrophobicity in the solenoid fragment and allows us to pinpoint “stopper” sequences, where local hydrophobicity quite closely resembles conditions encountered in globular proteins. Consequently, such fragments perform their function by mediating entropically advantageous contact with the water environment. We discuss examples of amyloid-like structures in solenoids, with particular attention to “stop” segments present in properly folded proteins found in living organisms.

The mechanism behind the selection of two different cleavage sites in NAG-NAM polymers.

Peptidoglycan is a giant molecule that forms the cell wall that surrounds bacterial cells. It is composed of alternating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) residues connected by β-(1,4)-glycosidic bonds and cross-linked with short polypeptide chains. Owing to the increasing antibiotic resistance against drugs targeting peptidoglycan synthesis, studies of enzymes involved in the degradation of peptidoglycan, such as N-acetylglucos-aminidases, may expose new, valuable drug targets. The scientific challenge addressed here is how lysozymes, muramidases which are likely to be the most studied enzymes ever, and bacterial N-acetylglucosaminidases discriminate between two glycosidic bonds that are different in sequence yet chemically equivalent in the same NAG-NAM polymers. In spite of more than fifty years of structural studies of lysozyme, it is still not known how the enzyme selects the bond to be cleaved. Using macromolecular crystallography, chemical synthesis and molecular modelling, this study explains how these two groups of enzymes based on an equivalent structural core exhibit a difference in selectivity. The crystal structures of Staphylococcus aureusN-acetylglucosaminidase autolysin E (AtlE) alone and in complex with fragments of peptidoglycan revealed that N-acetylglucosaminidases and muramidases approach the substrate at alternate glycosidic bond positions from opposite sides. The recognition pocket for NAM residues in the active site of N-acetylglucosaminidases may make them a suitable drug target.

Like-charged residues at the ends of oligoalanine sequences might induce a chain reversal.

We have examined the effect of like-charged residues on the conformation of an oligoalanine sequence. This was facilitated by circular dichroism (CD) and NMR spectroscopic and differential scanning calorimetric (DSC) measurements, and molecular dynamics calculations of the following three alanine-based peptides: Ac-K-(A)(5) -K-NH(2) (KAK5), Ac-K-(A)(4) -K-NH(2) (KAK4), Ac-K-(A)(3) -K-NH(2) (KAK3), where A and K denote alanine and lysine residues, respectively. Our earlier studies suggested that the presence of like-charged residues at the end of a short polypeptide chain composed of nonpolar residues can induce a chain reversal. For all three peptides, canonical molecular dynamics simulations with NMR-derived restraints demonstrate the presence of ensembles of structures with a tendency to form a chain reversal. The KAK3 peptide exhibits a bent shape with its ends close to each other, while KAK4 and KAK5 are more extended. In the KAK5 peptide, the lysine residues do not have any influence on each other and are very mobile. Nevertheless, the tendency to form a more or less pronounced chain reversal is observed and it seems to be stable in all three peptides. This chain reversal seems to be caused by screening of the nonpolar core from the solvent by the hydrated charged residues.

Structural Entropy to Characterize Small Proteins (70 aa) and Their Interactions

Proteins composed of short polypeptide chains (about 70 amino acid residues) participating in ligand-protein and protein-protein (small size) complex creation were analyzed and classified according to the hydrophobicity deficiency/excess distribution as a measure of structural and functional specificity and similarity. The characterization of this group of proteins is the introductory part to the analysis of the so called `Never Born Proteins' (NBPs) in search of protein compounds of biological activity in pharmacological context. The entropy scale (classification between random and deterministic limits) estimated according to the hydrophobicity irregularity organized in ranking list allows the comparative analysis of proteins under consideration. The comparison of the hydrophobicity deficiency/excess appeared to be useful for similarity recognition, examples of which are shown in the paper. The influence of mutations on structure and hydrophobicity distribution is discussed in detail.

Properties of the C-terminal Domain of Enzyme I of the Escherichia coli Phosphotransferase System

The bacterial phosphoenolpyruvate (PEP):glycose phosphotransferase system (PTS) mediates uptake/phosphorylation of sugars. The transport of all PTS sugars requires Enzyme I (EI) and a phosphocarrier histidine protein of the PTS (HPr). The PTS is stringently regulated, and a potential mechanism is the monomer/dimer transition of EI, because only the dimer accepts the phosphoryl group from PEP. EI monomer consists of two major domains, at the N and C termini (EI-N and EI-C, respectively). EI-N accepts the phosphoryl group from phospho-HPr but not PEP. However, it is phosphorylated by PEP(Mg(2+)) when complemented with EI-C. Here we report that the phosphotransfer rate increases approximately 25-fold when HPr is added to a mixture of EI-N, EI-C, and PEP(Mg(2+)). A model to explain this effect is offered. Sedimentation equilibrium results show that the association constant for dimerization of EI-C monomers is 260-fold greater than the K(a) for native EI. The ligands have no detectable effect on the secondary structure of the dimer (far UV CD) but have profound effects on the tertiary structure as determined by near UV CD spectroscopy, thermal denaturation, sedimentation equilibrium and velocity, and intrinsic fluorescence of the 2 Trp residues. The binding of PEP requires Mg(2+). For example, there is no effect of PEP on the T(m), an increase of 7 degrees C in the presence of Mg(2+), and approximately 14 degrees C when both are present. Interestingly, the dissociation constants for each of the ligands from EI-C are approximately the same as the kinetic (K(m)) constants for the ligands in the complete PTS sugar phosphorylation assays.

Cysteine-to-Serine Mutants of the Human Copper Chaperone for Superoxide Dismutase Reveal a Copper Cluster at a Domain III Dimer Interface

Cysteine-to-serine mutants of a maltose binding protein fusion with the human copper chaperone for superoxide dismutase (hCCS) were studied with respect to (i) their ability to transfer Cu to E,Zn superoxide dismutase (SOD) and (ii) their Zn and Cu binding and X-ray absorption spectroscopic (XAS) properties. Previous work has established that Cu(I) binds to four cysteine residues, two of which, C22 and C25, reside within an Atox1-like N-terminal domain (DI) and two of which, C244 and C246, reside in a short unstructured polypeptide chain at the C-terminus (DIII). The wild-type (WT) protein shows an extended X-ray absorption fine structure (EXAFS) spectrum characteristic of cluster formation, but it is not known how such a cluster is formed. Cys to Ser mutagenesis was used to investigate the Cu binding in more detail. Single Cys to Ser mutations, as represented by C22S and C244S, did little to affect the metal binding ratios of hCCS. Both mutants still showed approximately 2 Cu(I) ions and 1 Zn ion per protein. The double mutants C22/24S and C244/246S, on the other hand, showed Cu binding stoichiometries close to 1:1. The Zn-EXAFS of WT CCS showed a 3-4 histidine ligand environment that is consistent with Zn binding in the SOD-like domain II of CCS. The Zn environment remained unchanged between wild type and all of the mutant CCS proteins. Single Cys to Ser mutations displayed lower activity than WT protein, although close to full activity could be rescued by increasing the CCS:SOD ratios to 8:1 in the assay mixture. The structure of the Cu centers of the single mutants as revealed by EXAFS was also similar to that of WT protein, with clear indications of a Cu cluster. On the other hand, the double mutants showed a greater degree of perturbation. The DI C22/25S mutant was 70% active and formed a cluster with a more intense Cu-Cu interaction. The DIII C244/246S mutant retained only a fraction (16%) of activity and did not form a cluster. The results suggest the formation of a DIII-DIII cluster within a dimeric or tetrameric protein and further suggest that this cluster may be an important element of the copper transfer machinery.

Hylins: Bombinins H Structurally Related Peptides from the Skin Secretion of the Brazilian Tree-Frog Hyla biobeba

Two hemolytic peptides were isolated from the skin secretion of the Brazilian Hylidae frog Hyla biobeba, using reversed-phase chromatographic procedures. Hylins b1 and b2 exhibit short linear polypeptide chains, a large number of hydrophobic residues, amidated C termini and hemolytic properties. These two novel peptides are the first examples of bombinins H-like peptides isolated from anurans species not related to Bombina species.

Statistical mechanics of protein folding with separable energy functions.

We have initiated an entirely new approach to statistical mechanical models of strongly interacting systems where the configurational parameters and the potential energy function are both constructed so that the canonical partition function can be evaluated analytically. For a simplified model of proteins consisting of a single, fairly short polypeptide chain without cross-links, we can adjust the energy parameters to favor the experimentally determined native state of seven proteins having diverse types of folds. Then 497 test proteins are predicted to have stable native folds, even though they are also structurally diverse, and 480 of them have no significant sequence similarity to any of the training proteins.

Crystal Structure of Quinohemoprotein Amine Dehydrogenase from Pseudomonas putida: IDENTIFICATION OF A NOVEL QUINONE COFACTOR ENCAGED BY MULTIPLE THIOETHER CROSS-BRIDGES

The crystal structure of a quinohemoprotein amine dehydrogenase from Pseudomonas putida has been determined at 1.9-A resolution. The enzyme comprises three non-identical subunits: a four-domain alpha-subunit that harbors a di-heme cytochrome c, a seven-bladed beta-propeller beta-subunit that provides part of the active site, and a small gamma-subunit that contains a novel cross-linked, proteinous quinone cofactor, cysteine tryptophylquinone. More surprisingly, the catalytic gamma-subunit contains three additional chemical cross-links that encage the cysteine tryptophylquinone cofactor, involving a cysteine side chain bridged to either an Asp or Glu residue all in a hitherto unknown thioether bonding with a methylene carbon atom of acidic amino acid side chains. Thus, the structure of the 79-residue gamma-subunit is quite unusual, containing four internal cross-links in such a short polypeptide chain that would otherwise be difficult to fold into a globular structure.

Value of circulating immune parameters in renal transplantation

Diagnosis of acute kidney graft rejection is based on conventional parameters such as creatinine (Crea), Crea-clearance, body temperature, urinary volume, body weight. Taken together they are inexpensive, noninvasive and attain a relatively high sensitivity. In many patients, however, kidney biopsies have to be obtained to ascertain the presence of acute rejection. The presence or absence of rejection might also be authenticated by monitoring serum immune parameters, capable of predicting the onset of clinically relevant immunologic activity. This would provide information on the response to antirejection therapy before graft dysfunction becomes clinically manifest. The following parameters were selected based on their specific characteristics: • ⊎ c-ICAM-1 (intercellular adhesion molecule). Allograft transplantation leads to a chronic or acute immune response that is related to increased expression and release of c-ICAM-1. c-ICAM-1 is expressed on almost all cell types, including macrophages, T- and B-lymphocytes during activation, as well as unstimulated vascular endothelial cells. Healthy individuals show a mean serum level of 230 (130 to 300) ng/mL. • ⊎ s-TNF-R (tumour-necrosis-factor receptor). Elevated s-TNF-R levels are observed in any type of immune response but also eventuate in acute or chronic renal failure as a retention phenomenon. s-TNF-R binds with high affinity and specificity to TNF and acts as an immunobiological regulator of the pluripotent TNF-mediated functions. The complete receptor molecule is expressed on fibroblasts, endothelial cells (EC), myeloid cells, as well as on mitogen-stimulated lymphocytes. • ⊎ s-IL2-R (interleukin-2-receptor). Monoclonal antibodies to IL2-R inhibit T-cell proliferation and counteract renal allograft rejection. IL2-R-bearing cells are crucial in graft rejection, and agents that kill these cells boost graft survival: anti-IL2-R antibodies administered prophylactically to renal allograft patients reduce the rate of early graft rejection. Its mean level in normal individuals is 256 ± 112 U/mL. • ⊎ Neopterin. Is significantly related to T-cell-mediated pathologies and, therefore, can provide clinically useful information on infection, cancer, autoimmunity and graft rejection. Neopterin release from renal epithelial cells has been shown to be stimulated by IFN-γ. Its mean serum level in normal individuals is 5.4 ± 2.3 nmol/L. • ⊎ s-MHC-1 (major histocompatibility complex). Consists of a 44,000-kD intracellular and a short extracellular polypeptide chain designated β2-microglobulin (β2-MG). MHC-1 is the receptor for CD8 + cytotoxic T cells, with the amount of MHC products apparently determining the susceptibility of target cells to being lysed. • ⊎ ELAM-1 (endothelial leukocyte adhesion molecule). Is a glycoprotein (E-selectin) expressed on cytokine-activated (TNF-alpha, IL2, LPS) endothelial cells. Endothelial cells constitute the interface between allograft and the host's immune system. Endothelial cell functions play a pivotal role in inflammatory responses and vessel behaviour, and might assume a pathogenic role in allograft rejection. E-selectin is the most likely mediator of initial lymphocyte binding to endothelial cells by mediating, in contrast to the integrins, adhesion of resting lymphocytes. The ligands for ELAM-1 are carbohydrates. The present study was performed to establish (1) potential correlations of these parameters with the course of rejection, infection, or of stable condition, in renal allograft recipients and (2) whether antirejection therapy is capable of influencing these parameters. As noninvasive methods for measuring target-organ levels of cytokines or inflammatory markers are not available, a critical appraisal of the sensitivity and specificity of these parameters in peripheral blood during graft rejection appears warranted.

Three antigenic regions in p17 of human immunodeficiency virus type 1 (HIV-1) revealed by mouse monoclonal antibodies and human antibodies in HIV-1 carrier sera.

We investigated the murine antibody response to recombinant p17 (rp17) of human immunodeficiency virus type 1 (HIV-1) and the human antibody response directed to p17 in HIV-1 infection. Three large peptides covering residues 12-29, 53-87 and 87-115 of p17 were synthesized. The cysteine residues 57 and 87 of peptide 53-87 were reoxidized to form a disulfide bridge. Eighteen out of 19 murine monoclonal anti-rp17 antibodies had relatively high affinities (KA = 1.9 x 10(5)-1.4 x 10(8) M-1) with one of the 3 p17 peptides in the liquid phase. Each monoclonal antibody reacted only with one particular peptide and had no reactivity with the other 2 p17 peptides. All the monoclonal antibodies reacted with rp17 in the liquid phase with a reasonable degree of affinity (KA = 2.0 x 10(5)-1.8 x 10(7) M-1). Four HIV-1 carrier sera, which were positive in ELISA using rp17 as the antigen, reacted positively in an ELISA using 3 p17 peptides which were used to titrate murine monoclonal antibodies. Murine monoclonal antibodies having specificity for the 3 p17 peptides stained live HIV-1-infected cells by means of indirect membrane immunofluorescence, irrespective of their specificity. This suggests that the various portions of p17 (at least 3 regions of p17) were exposed on the surface of live infected cells, probably as short polypeptide chains.

Fluctuations in molecular size, entanglement complexity, and anisometry along molecular dynamics trajectories of short α‐helices

AbstractWe present a detailed study of the intrinsic shape stability of short flexible polypeptide chains by using a number of distinct descriptors. Some large‐scale structural features found in macromolecular folding—unfolding dynamics can be monitored in terms of molecular size and compactness. Similarly, one could employ descriptors of anisometry to that purpose. In addition, we have recently proposed a new family of global, absolute shape descriptors to quantify the complexity of the self‐entanglements in a polymer, or, loosely, its “degree of folding.” This latter aspect of the molecular shape is characterized by combining simple geometrical and topological properties of the α‐carbon backbone. The resulting descriptor, the probability of observing a rigid backbone as a projected curve exhibiting N overcrossings, has been employed already for the analysis of molecular dynamics of linear hydrocarbons and aliphatic carboxylic acids. In this work, three distinct properties of a molecular chain are monitored simultaneously, for the first lime, along computer‐simulated dynamic trajectories: size, anisotropy, and entanglements. The systems studied are a series of 3 polypeptide helices: 10‐polyalanine, 10‐polyvaline, and 10‐polyglycine. Constant temperature trajectories have been computed for these helices, at thermal equilibrium with a simulated external bath, with temperatures ranging from 300 to 700 K. The differential structural stability of the helices is assessed from the various viewpoints. Even though the systems are simple, they contain some of the essential features expected in polypeptides of relevance to structural biology. The results show that the, descriptors of anisometry and entanglements are rather independent. For instance, it is found that, contrary to intuition the unfolding of helices may involve nonhelical “coil” configurations that are both self‐entangled and prolate. The simultaneous study of independent shape descriptors provides a new picture of the nature of conformations found during dynamics trajectories. The resulting description characterizes a polymer conformation in a absolute terms, and not relative to an ad hoc reference structure. The proposed approach gives some insights into the stability of secondary structural motifs in proteins and the mechanisms involved into their formation or unfolding. © 1995 John Wiley & Sons, Inc.

Evolution of Genetic Information Flow From the Viewpoint of Protein Sequence Similarity

As a course of inquiry into the evolution of genetic information flow, similarity relations of amino acid sequences between the proteins involved in translation, transcription and replication are investigated. The sequence data of these proteins are mostly accumulated from Escherichia coli, and the present investigation is carried out mainly on this organism by the FASTP program. This result reveals an interesting similarity linkage extending from ribosomal proteins to the proteins participating in translational elongation process and to the proteins in transcription and replication. Although the ribosomal proteins are of relatively short polypeptide chains, our systematic comparison between these proteins finds many similarity relations, being more than 100 in terms of "overlap", reducing them to about 14 elementary ribosomal proteins from which other ribosomal proteins would have diverged. Moreover, the proteins involved in translation, transcription and replication contain the regions similar to the elementary ribosomal proteins. In particular, some initiation and elongation factors in translation process are assigned to be similar to the elementary ribosomal proteins almost over the whole regions. To such an elongation factor Tu, the α and σ 70 subunits of RNA polymerase and primase also show similarity in the wider regions than the individual ribosomal proteins, and they are shown to be fundamental for the similarity linkage extending to the other polypeptide chains involved in transcription and replication processes, although the latter polypeptide chains contain regions not similar to any ribosomal protein. This divergence pattern of similarity relations strongly suggests that the proteins involved in the contemporary genetic information flow DNA → RNA → protein have evolved from some elementary fibosomal proteins, first by gene fusion, in a primitive organism of the RNA-protein world, and then by the addition of the mechanism of domain shuffling from other genes in the DNA-RNA-protein world.

Polypeptide: From DNA and mRNA synthesis to a short polypeptide chain

Polypeptide: From DNA and mRNA synthesis to a short polypeptide chain

Monte Carlo simulation of the conformational behaviour of a polypeptide chain near a charged surface

The conformational behaviour of a short polypeptide chain in the neighbourhood of a charged plane is simulated using a Monte Carlo method. In this approach, the plane is taken as a model of an interface separating a hydrophobic region from a hydrophilic one. It is shown that in the neighbourhood of the plane, folded molecular conformations are prevailing whilst stretched conformations are preferred far from the interface. When the plane is not charged, the molecule adjusts itself parallel to the interface. For a given position of the molecule with respect to the plane, when the charge density of the plane is increased, the molecule tends to turn perpendicular to the plane. The surface may either attract or repulse the molecule depending on the value of the charge density (the plane is always negatively charged).