Polypeptide dynamics: Experimental tests of an optimized Rouse–Zimm type model

Hu, Yi; MacInnis, Jean M.; Cherayil, Binny J.; Fleming, Graham R.; Freed, Karl F.; Perico, Angelo

doi:10.1063/1.459452

Cited by 39 publications

(29 citation statements)

References 34 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our MC moves correspond to the motion of a statistical segment length (b). For Rouse-Zimm dynamics, the time for local MC moves scales as b 2 (17,18). Estimates of the value of b for synthetic polymers lead us to conclude that the microscopic time corresponding to our simulations is 10 Ϫ8 to 10 Ϫ9 sec [in agreement with previous estimates (19,20)].…”

Section: Phenomenology Of Statistical Pattern Matchingsupporting

confidence: 76%

See 1 more Smart Citation

Simulation of biomimetic recognition between polymers and surfaces

Golumbfskie

Pande

Chakraborty

1999

Proc. Natl. Acad. Sci. U.S.A.

101

View full text Add to dashboard Cite

Many biological processes, such as transmembrane signaling and pathogen-host interactions, are initiated by a protein recognizing a specific pattern of binding sites on part of a membrane or cell surface. By recognition, we imply that the polymer quickly finds and then adsorbs strongly on the pattern-matched region and not on others. The development of synthetic systems that can mimic such recognition between polymers and surfaces could have significant impact on advanced applications such as the development of sensors, molecular-scale separation processes, and synthetic viral inhibition agents. Attempting to affect recognition in synthetic systems by copying the detailed chemistries to which nature has been led over millenia of evolution does not seem practical for most applications. This leads us to the following question: Are there any universal strategies that can affect recognition between polymers and surfaces? Such generic strategies may be easier to implement in abiotic applications. We describe results that suggest that biomimetic recognition between synthetic polymers and surfaces is possible by exploiting certain generic strategies, and we elucidate the kinetic mechanisms by which this occurs. Our results suggest convenient model systems for experimental studies of dynamics in free energy landscapes characteristic of frustrated systems. It is common in biology for a protein to recognize and bind to a specific pattern of binding sites localized in a region of a surface. It is not our purpose to explain how the intricate chemistries resulting from evolution allow such specific recognition to occur. Rather, in this paper, we explore whether there are minimal universal strategies that would allow synthetic polymers to mimic recognition. Such strategies might be profitably exploited in applications (1, 2). To deduce candidates for such strategies, we were inspired by some coarse-grained observations regarding biological systems. Proteins are composed of many types of monomers and have sequences that are not periodically repeating (3-6). Similarly, the pattern of different binding sites on cell surfaces is not periodically repeating. These observations led us to ask whether competing interactions (because of preferential interactions between different types of monomers and surface sites) and disorder are essential ingredients for biomimetic recognition in synthetic systems. [We note that Muthukumar (7,8) has also thought about questions pertinent to pattern recognition between polymers and surfaces, and Khokhlov and coworkers (9) have considered designing polymer sequences for efficient binding to uniform surfaces that do not bear patterns.] Disordered heteropolymers (DHPs) are synthetic macromolecules with chemically different monomer units distributed along the backbone in a disordered sequence that is described statistically. ʈ Like proteins, they are composed of different monomers, with sequences that are aperiodic and quenched (the sequences cannot change in response to the environment). Unlike protei...

show abstract

Section: Phenomenology Of Statistical Pattern Matchingsupporting

confidence: 76%

“…1, the DHPs do adsorb onto **On the monomeric scale, local motions occur in 10 Ϫ10 to 10 Ϫ11 sec, depending on solvent viscosity and monomer size (17,18). Our MC moves correspond to the motion of a statistical segment length (b).…”

Section: Phenomenology Of Statistical Pattern Matchingmentioning

confidence: 99%

Simulation of biomimetic recognition between polymers and surfaces

Golumbfskie

Pande

Chakraborty

1999

Proc. Natl. Acad. Sci. U.S.A.

101

View full text Add to dashboard Cite

show abstract

“…Furthermore, the average c values (2.1 and 3.3 ns, calculated with and without R ex respectively) are barely a factor of 10 greater than the average e values (0.19 and 0.25 ns), and in some cases the errors in the internal and overall correlation times overlap. Both of these observations support the notion that HIV-1 Tat-(1-72) exists in a random coil conformation in which there is no clear separation of internal and overall rotational correlation times (97).…”

supporting

confidence: 76%

“…As indicated in Fig. 4a, the steady-state heteronuclear NOEs measured at 600 and 800 MHz exhibit a relatively featureless, flattened bell-shaped variation with amino acid sequence, as expected for an unfolded protein (97). The NOEs range from Ϫ3.3 (Ϫ2.6) to Ϫ0.60 (Ϫ0.41) with mean values of Ϫ1.27 (Ϫ0.933) at 600 MHz (and 800 MHz).…”

Section: Nmr Resonance Assignments-sequentialmentioning

confidence: 89%

HIV-1 Tat Is a Natively Unfolded Protein

Shojania

O'Neil

2006

Journal of Biological Chemistry

118

View full text Add to dashboard Cite

Human immunodeficiency virus type 1 (HIV-1) 2 -infected resting CD4 ϩ memory T-cells form a persistent viral reservoir that is a major barrier to curing HIV-1 infection although they do not permit viral replication (1). A small, RNA-binding protein, Tat (transactivator of transcription) (2), plays a central role in the regulation of HIV-1 replication and in potential approaches to treating latently infected cells. During transcription of the viral DNA, RNA polymerase II stalls as a result of binding the negative transcription elongation factor, resulting in the production of prematurely terminated transcripts that may include the tat message (3). Following translation, the Tat protein is transported from the cytoplasm into the nucleus, where it binds a stem-loop structure (transactivation response element (TAR)) formed by the first 59 nucleotides of the HIV-1 RNA (4). Tat stimulates elongation of full-length transcripts by recruiting the positive transcription elongation factor b, a complex of a regulatory cyclin and cyclin-dependent kinase 9, that phosphorylates the C-terminal domain of RNA polymerase II, components of negative transcription elongation factor, and the transcription elongation factor Spt5 (5-7). Recent results suggest that Tat activates positive transcription elongation factor b by displacing Hexim1 (hexamethylene bisacetamide-inducible protein 1) from its cyclin T1 binding site (8) and that the affinity of the Tat-cyclin T1-cyclindependent kinase 9 complex for TAR is regulated through Tat acetylation by histone acetyltransferases (9, 10). The absence of Tat and low levels of cyclin-dependent kinase 9 and cyclin T1 in resting CD4ϩ T-cells are both implicated in HIV-1 latency (1). Tat may also be involved in derepression of heterochromatin, transcription initiation (11), and reverse transcription (12). In addition to its intracellular activities, the literature contains a plethora of reports of extracellular Tat activities, including general cytotoxicity, that may contribute to immune suppression (13,14) and the development of HIV-dementia (15). A molecular understanding of Tat activity requires a determination of its structure and interactions with cellular and viral partners (16, 17). HIV-1 Tat is a 101-residue protein encoded by two exons (3, 18). The first exon defines amino acids 1-72 that encompass an acidic and proline-rich N terminus (amino acids 1-21), a cysteine-rich region (amino acids 22-37), a core (amino acids 38 -47), a basic region (amino acids 48 -57), and a Gln-rich segment (amino acids 58 -72) (19); it activates transcription with the same proficiency as the full-length protein (3, 20 -22). Residues 1-24 form the co-activator and acetyltransferase CREB-binding protein KIX domain binding site (17). Cyclin T1 is thought to interact with the Cys-rich region of Tat (23), and mutation of any one of six of the seven Cys residues results in inactivation (3). The end of the Cys-rich region and the core are involved in mitochondrial apoptosis of bystander noninfected cells through thei...

show abstract

“…5,6 Side-chain flexibility and fluctuations in the peptide backbone lead to internal motions in peptides. We have used measurements of the temperature dependence of the reorientational friction 7 to expose intramolecular dynamics in short peptides.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine and peptide reorientational mobility in polymer solutions: Time‐dependent fluorescence anisotropy measurements

2003

View full text Add to dashboard Cite

The ability of peptides to form biologically active conformations that bind to receptors is governed by their dynamics and their propensity to form stable structures. Such factors are consequently important in the design of peptide drugs. Moreover, the stability of such peptides depends on interactions of the peptide with the surrounding matrix. In this article, we study the effect of the polymer poly(vinyl pyrrolidone) (PVP) on the mobility and orientational dynamics of tyrosine and a model peptide, Val-Tyr-Pro-Asn-Gly-Ala (VYPNGA) in glycerol-water solutions. Orientational dynamics are studied experimentally by time-resolved fluorescence anisotropy decays of tyrosine. The presence of PVP leads to the possibility of a distribution of environments for the peptide. The orientational dynamics of tyrosine show that the probe molecule experiences two very different environments. In one, tyrosine rotational motion is weakly coupled to PVP, while in the other, tyrosine interacts strongly with PVP leading to much slower rotational times. The dynamics of VYPNGA are more complex. Fast intramolecular, localized reorientations of the tyrosine are detected. The temperature dependence of the reorientational dynamics of the tyrosine side chain reveal that these motions are shielded from solvent friction. In contrast, global motions of the peptide are severely restricted by PVP, suggesting the ability of the polymer to restrict peptide mobility.

show abstract

Polypeptide dynamics: Experimental tests of an optimized Rouse–Zimm type model

Cited by 39 publications

References 34 publications

Simulation of biomimetic recognition between polymers and surfaces

Simulation of biomimetic recognition between polymers and surfaces

HIV-1 Tat Is a Natively Unfolded Protein

Tyrosine and peptide reorientational mobility in polymer solutions: Time‐dependent fluorescence anisotropy measurements

Contact Info

Product

Resources

About