Collapse Transitions of Proteins and the Interplay Among Backbone, Sidechain, and Solvent Interactions

2018 ◽  
Vol 47 (1) ◽  
pp. 19-39 ◽  
Author(s):  
Alex S. Holehouse ◽  
Rohit V. Pappu
Keyword(s):  
Aqueous Solutions ◽  
Driving Forces ◽  
Three Dimensional ◽  
Polymer Physics ◽  
Solvent Interactions ◽  
Intrinsically Disordered ◽  
The Past ◽  
Collapse Transitions

Proteins can collapse into compact globules or form expanded, solvent-accessible, coil-like conformations. Additionally, they can fold into well-defined three-dimensional structures or remain partially or entirely disordered. Recent discoveries have shown that the tendency for proteins to collapse or remain expanded is not intrinsically coupled to their ability to fold. These observations suggest that proteins do not have to form compact globules in aqueous solutions. They can be intrinsically disordered, collapsed, or expanded, and even form well-folded, elongated structures. This ability to decouple collapse from folding is determined by the sequence details of proteins. In this review, we highlight insights gleaned from studies over the past decade. Using a polymer physics framework, we explain how the interplay among sidechains, backbone units, and solvent determines the driving forces for collapsed versus expanded states in aqueous solvents.

Mitochondrial Reconstructions Based on Serial Thick Sections and HVEM

1975 ◽  
Vol 33 ◽  
pp. 286-287
Author(s):  
Jerome J. Paulin
Keyword(s):  
Imaging Techniques ◽  
Three Dimensional ◽  
Posterior Pole ◽  
Dimensional Structure ◽  
Stereo Imaging ◽  
Thin Sections ◽  
Anatomical Features ◽  
The Past ◽  
Cellular Components ◽  
Mitochondrial Reticulum

Within the past decade it has become apparent that HVEM offers the biologist a means to explore the three-dimensional structure of cells and/or organelles. Stereo-imaging of thick sections (e.g. 0.25-10 μm) not only reveals anatomical features of cellular components, but also reduces errors of interpretation associated with overlap of structures seen in thick sections. Concomitant with stereo-imaging techniques conventional serial Sectioning methods developed with thin sections have been adopted to serial thick sections (≥ 0.25 μm). Three-dimensional reconstructions of the chondriome of several species of trypanosomatid flagellates have been made from tracings of mitochondrial profiles on cellulose acetate sheets. The sheets are flooded with acetone, gluing them together, and the model sawed from the composite and redrawn.The extensive mitochondrial reticulum can be seen in consecutive thick sections of (0.25 μm thick) Crithidia fasciculata (Figs. 1-2). Profiles of the mitochondrion are distinguishable from the anterior apex of the cell (small arrow, Fig. 1) to the posterior pole (small arrow, Fig. 2).

scholarly journals Binding Ensembles of p53-MDM2 Peptide Inhibitors by Combining Bayesian Inference and Atomistic Simulations

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 198
Author(s):  
Lijun Lang ◽  
Alberto Perez
Keyword(s):  
Bayesian Inference ◽  
Virtual Screening ◽  
Statistical Mechanics ◽  
Small Molecules ◽  
Rational Design ◽  
Driving Forces ◽  
Peptide Inhibitors ◽  
Atomistic Simulations ◽  
Binding Mechanism ◽  
Intrinsically Disordered

Designing peptide inhibitors of the p53-MDM2 interaction against cancer is of wide interest. Computational modeling and virtual screening are a well established step in the rational design of small molecules. But they face challenges for binding flexible peptide molecules that fold upon binding. We look at the ability of five different peptides, three of which are intrinsically disordered, to bind to MDM2 with a new Bayesian inference approach (MELD × MD). The method is able to capture the folding upon binding mechanism and differentiate binding preferences between the five peptides. Processing the ensembles with statistical mechanics tools depicts the most likely bound conformations and hints at differences in the binding mechanism. Finally, the study shows the importance of capturing two driving forces to binding in this system: the ability of peptides to adopt bound conformations (ΔGconformation) and the interaction between interface residues (ΔGinteraction).

scholarly journals Midface Reconstruction: Planning and Outcome

2020 ◽  
Vol 53 (03) ◽  
pp. 324-334
Author(s):  
Gautam Biswas
Keyword(s):  
Digital Imaging ◽  
3D Structure ◽  
Three Dimensional ◽  
The Past ◽  
Complex Anatomy ◽  
Osseointegrated Implants ◽  
Low Profile ◽  
3D Printed ◽  
Midface Reconstruction ◽  
Reconstruction Planning

Abstract Reconstruction of the complex anatomy and aesthetics of the midface is often a challenge. A careful understanding of this three-dimensional (3D) structure is necessary. Anticipating the extent of excision and its planning following oncological resections is critical.In the past over two decades, with the advances in microsurgical procedures, contributions toward the reconstruction of this area have generated interest. Planning using digital imaging, 3D printed models, osseointegrated implants, and low-profile plates, has favorably impacted the outcome. However, there are still controversies in the management: to use single composite tissues versus multiple tissues; implants versus autografts; vascularized versus nonvascularized bone; prosthesis versus reconstruction.This article explores the present available options in maxillary reconstruction and outlines the approach in the management garnered from past publications and experiences.

scholarly journals Deciphering the Role of Residues Involved in Disorder-To-Order Transition Regions in Archaeal tRNA Methyltransferase 5

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 399
Author(s):  
Ambuj Srivastava ◽  
Dhanusha Yesudhas ◽  
Shandar Ahmad ◽  
M. Michael Gromiha
Keyword(s):  
Three Dimensional ◽  
Md Simulations ◽  
Order Transition ◽  
Free Form ◽  
Wild Type ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Type Complex ◽  
In The Wild ◽  
Trna Methyltransferase

tRNA methyltransferase 5 (Trm5) enzyme is an S-adenosyl methionine (AdoMet)-dependent methyltransferase which methylates the G37 nucleotide at the N1 atom of the tRNA. The free form of Trm5 enzyme has three intrinsically disordered regions, which are highly flexible and lack stable three-dimensional structures. These regions gain ordered structures upon the complex formation with tRNA, also called disorder-to-order transition (DOT) regions. In this study, we performed molecular dynamics (MD) simulations of archaeal Trm5 in free and complex forms and observed that the DOT residues are highly flexible in free proteins and become stable in complex structures. The energetic contributions show that DOT residues are important for stabilising the complex. The DOT1 and DOT2 are mainly observed to be important for stabilising the complex, while DOT3 is present near the active site to coordinate the interactions between methyl-donating ligands and G37 nucleotides. In addition, mutational studies on the Trm5 complex showed that the wild type is more stable than the G37A tRNA mutant complex. The loss of productive interactions upon G37A mutation drives the AdoMet ligand away from the 37th nucleotide, and Arg145 in DOT3 plays a crucial role in stabilising the ligand, as well as the G37 nucleotide, in the wild-type complex. Further, the overall energetic contribution calculated using MMPBSA corroborates that the wild-type complex has a better affinity between Trm5 and tRNA. Overall, our study reveals that targeting DOT regions for binding could improve the inhibition of Trm5.

scholarly journals Substrate-independent three-dimensional polymer nanosheets induced by solution casting

2021 ◽  
Author(s):  
Cheol Hun Park ◽  
Eun Min Go ◽  
Kyung Min Lee ◽  
Chang Soo Lee ◽  
Sang Kyu Kwak ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Simple Solution ◽  
Solution Casting ◽  
Solvent Interactions ◽  
Comb Copolymer ◽  
Substrate Independent ◽  
Polymer Solvent

Unprecedented substrate-independent polymeric 3D nanosheets were induced via simple solution casting using PEGBEM–POEM comb copolymer. A possible mechanism is the change in the polymer–solvent interactions on the surface.

scholarly journals The Study of Three-Dimensional Fingerprint Recognition in Cultural Heritage

2021 ◽  
Vol 14 (4) ◽  
pp. 1-20
Author(s):  
Dzemila Sero ◽  
Isabelle Garachon ◽  
Erma Hermens ◽  
Robert Van Liere ◽  
Kees Joost Batenburg
Keyword(s):  
Image Processing ◽  
Cultural Heritage ◽  
Three Dimensional ◽  
Fingerprint Recognition ◽  
Person Identification ◽  
Imaging Technologies ◽  
The Past ◽  
Reconstruction Methods ◽  
Cultural Systems ◽  
Digital Fingerprint

Fingerprints play a central role in any field where person identification is required. In forensics and biometrics, three-dimensional fingerprint-based imaging technologies, and corresponding recognition methods, have been vastly investigated. In cultural heritage, preliminary studies provide evidence that the three-dimensional impressions left on objects from the past (ancient fingerprints) are of paramount relevance to understand the socio-cultural systems of former societies, to possibly identify a single producer of multiple potteries, and to authenticate the artist of a sculpture. These findings suggest that the study of ancient fingerprints can be further investigated and open new avenues of research. However, the potential for capturing and analyzing ancient fingerprints is still largely unexplored in the context of cultural heritage research. In fact, most of the existing studies have focused on plane fingerprint representations and commercial software for image processing. Our aim is to outline the opportunities and challenges of digital fingerprint recognition in answering a range of questions in cultural heritage research. Therefore, we summarize the fingerprint-based imaging technologies, reconstruction methods, and analyses used in biometrics that could be beneficial to the study of ancient fingerprints in cultural heritage. In addition, we analyze the works conducted on ancient fingerprints from potteries and ceramic/fired clay sculptures. We conclude with a discussion on the open challenges and future works that could initiate novel strategies for ancient fingerprint acquisition, digitization, and processing within the cultural heritage community.

scholarly journals Disorder in a two-domain neuronal Ca2+-binding protein regulates domain stability and dynamics using ligand mimicry

2020 ◽  
Author(s):  
Lasse Staby ◽  
Katherine R. Kemplen ◽  
Amelie Stein ◽  
Michael Ploug ◽  
Jane Clarke ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Three Dimensional ◽  
Life Time ◽  
Disordered Proteins ◽  
Intrinsically Disordered ◽  
Order And Disorder ◽  
C Terminus ◽  
Close Relationship ◽  
Stability Dynamics ◽  
And Function

Abstract Understanding the interplay between sequence, structure and function of proteins has been complicated in recent years by the discovery of intrinsically disordered proteins (IDPs), which perform biological functions in the absence of a well-defined three-dimensional fold. Disordered protein sequences account for roughly 30% of the human proteome and in many proteins, disordered and ordered domains coexist. However, few studies have assessed how either feature affects the properties of the other. In this study, we examine the role of a disordered tail in the overall properties of the two-domain, calcium-sensing protein neuronal calcium sensor 1 (NCS-1). We show that loss of just six of the 190 residues at the flexible C-terminus is sufficient to severely affect stability, dynamics, and folding behavior of both ordered domains. We identify specific hydrophobic contacts mediated by the disordered tail that may be responsible for stabilizing the distal N-terminal domain. Moreover, sequence analyses indicate the presence of an LSL-motif in the tail that acts as a mimic of native ligands critical to the observed order–disorder communication. Removing the disordered tail leads to a shorter life-time of the ligand-bound complex likely originating from the observed destabilization. This close relationship between order and disorder may have important implications for how investigations into mixed systems are designed and opens up a novel avenue of drug targeting exploiting this type of behavior.

Design and Marker-Based Validation of a Biplane Fluoroscopy System for Studying the Foot and Ankle

2012 ◽  
Author(s):  
Joseph M. Iaquinto ◽  
Richard Tsai ◽  
Michael J. Fassbind ◽  
David R. Haynor ◽  
Bruce J. Sangeorzan ◽  
...  
Keyword(s):  
Precise Measurement ◽  
Three Dimensional ◽  
The Body ◽  
Initial Evaluation ◽  
Foot And Ankle ◽  
Research Groups ◽  
The Past ◽  
Model Based ◽  
Biplane Fluoroscopy ◽  
Model Based Analysis

The ability to accurately measure three dimensional (3D) bone kinematics is key to understanding the motion of the joints of the body, and how such motion is altered by injury, disease, and treatment. Precise measurement of such kinematics is technically challenging. Biplane fluoroscopy is ideally suited to measure bone motion. Such systems have been developed in the past for both radiographic stereo-photogrammetric analysis (RSA) [1] and the more challenging model-based analysis [2]. Research groups have studied the knee [3,4], shoulder [5] and ankle [6] motion with similar techniques. The work presented here is an initial evaluation of the performance of our system, i.e., a validation that this in-house system can detect magnitudes of motion on-par with other existing systems.

Sign in / Sign up

Export Citation Format

Share Document