Molecular Dynamics Simulations of the Oil-Detachment from the Hydroxylated Silica Surface: Effects of Surfactants, Electrostatic Interactions, and Water Flows on the Water Molecular Channel Formation

2018 ◽  
Vol 122 (6) ◽  
pp. 1905-1918 ◽  
Author(s):  
Jian Tang ◽  
Zhou Qu ◽  
Jianhui Luo ◽  
Lanyan He ◽  
Pingmei Wang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Electrostatic Interactions ◽  
Silica Surface ◽  
Surface Effects ◽  
Channel Formation ◽  
Water Flows ◽  
Dynamics Simulations ◽  
Molecular Channel

scholarly journals SLC6A14, a Pivotal Actor on Cancer Stage: When Function Meets Structure

2019 ◽  
Vol 24 (9) ◽  
pp. 928-938 ◽  
Author(s):  
Luca Palazzolo ◽  
Chiara Paravicini ◽  
Tommaso Laurenzi ◽  
Sara Adobati ◽  
Simona Saporiti ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Electrostatic Interactions ◽  
Amino Acid Residues ◽  
Dibasic Amino Acid ◽  
Novel Target ◽  
Function Relationship ◽  
Dynamics Simulations

SLC6A14 (ATB0,+) is a sodium- and chloride-dependent neutral and dibasic amino acid transporter that regulates the distribution of amino acids across cell membranes. The transporter is overexpressed in many human cancers characterized by an increased demand for amino acids; as such, it was recently acknowledged as a novel target for cancer therapy. The knowledge on the molecular mechanism of SLC6A14 transport is still limited, but some elegant studies on related transporters report the involvement of the 12 transmembrane α-helices in the transport mechanism, and describe structural rearrangements mediated by electrostatic interactions with some pivotal gating residues. In the present work, we constructed a SLC6A14 model in outward-facing conformation via homology modeling and used molecular dynamics simulations to predict amino acid residues critical for substrate recognition and translocation. We docked the proteinogenic amino acids and other known substrates in the SLC6A14 binding site to study both gating regions and the exposed residues involved in transport. Interestingly, some of these residues correspond to those previously identified in other LeuT-fold transporters; however, we could also identify a novel relevant residue with such function. For the first time, by combined approaches of molecular docking and molecular dynamics simulations, we highlight the potential role of these residues in neutral amino acid transport. This novel information unravels new aspects of the human SLC6A14 structure–function relationship and may have important outcomes for cancer treatment through the design of novel inhibitors of SLC6A14-mediated transport.

scholarly journals Effect of Ca2+ on the promiscuous target-protein binding mechanism of calmodulin

2018 ◽  
Author(s):  
Annie M. Westerlund ◽  
Lucie Delemotte
Keyword(s):  
Molecular Dynamics ◽  
Protein Binding ◽  
Molecular Dynamics Simulations ◽  
Electrostatic Interactions ◽  
Solvent Exposure ◽  
Conformational States ◽  
Hydrophobic Residues ◽  
Target Proteins ◽  
Flexible Mechanism ◽  
Dynamics Simulations

AbstractCalmodulin (CaM) is a calcium sensing protein that regulates the function of a large number of proteins, thus playing a crucial part in many cell signaling path- ways. CaM has the ability to bind more than 300 different target peptides in a Ca2+-dependent manner, mainly through the exposure of hydrophobic residues. How CaM can bind a large number of targets while retaining some selectivity is a fascinating open question.Here, we explore the mechanism of CaM selective promiscuity for selected target proteins. Analyzing enhanced sampling molecular dynamics simulations of Ca2+-bound and Ca2+-free CaM via spectral clustering has allowed us to identify distinct conformational states, characterized by interhelical angles, secondary structure determinants and the solvent exposure of specific residues. We searched for indicators of conformational selection by mapping solvent exposure of residues in these conformational states to contacts in structures of CaM/target peptide complexes. We thereby identified CaM states involved in various binding classes arranged along a depth binding gradient. Binding Ca2+ modifies the accessible hydrophobic surface of the two lobes and allows for deeper binding. Apo CaM indeed shows shallow binding involving predominantly polar and charged residues. Furthermore, binding to the C-terminal lobe of CaM appears selective and involves specific conformational states that can facilitate deep binding to target proteins, while binding to the N-terminal lobe appears to happen through a more flexible mechanism. Thus the long-ranged electrostatic interactions of the charged residues of the N-terminal lobe of CaM may initiate binding, while the short-ranged interactions of hydrophobic residues in the C-terminal lobe of CaM may account for selectivity.This work furthers our understanding of the mechanism of CaM binding and selectivity to different target proteins and paves the way towards a comprehensive model of CaM selectivity.Author summaryCalmodulin is a protein involved in the regulation of a variety of cell signaling pathways. It acts by making usually calcium-insensitive proteins sensitive to changes in the calcium concentration inside the cell. Its two lobes bind calcium and allow the energetically unfavorable exposure of hydrophobic residues to the aqueous environment which can then bind target proteins. The mechanisms behind the simultaneous specificity and variation of target protein binding is yet unknown but will aid understanding of the calcium-signaling and regulation that occur in many of our cellular processes.Here, we used molecular dynamics simulations and data analysis techniques to investigate what effect calcium has on the binding modes of calmodulin. The simulations and analyses allow us to observe and differentiate specific states. One domain of calmodulin is shown to be selective with binding involving short- distance interactions between hydrophobic residues, while the other binds target proteins through a more flexible mechanism involving long-distance electrostatic interactions.

Parameterization of electrostatic interactions for molecular dynamics simulations of heterocyclic polymers

2015 ◽  
Vol 53 (13) ◽  
pp. 912-923 ◽  
Author(s):  
Victor M. Nazarychev ◽  
Sergey V. Larin ◽  
Alexander V. Yakimansky ◽  
Natalia V. Lukasheva ◽  
Andrey A. Gurtovenko ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Electrostatic Interactions ◽  
Heterocyclic Polymers ◽  
Dynamics Simulations

scholarly journals Adsorption of Fibronectin Fragment on Surfaces Using Fully Atomistic Molecular Dynamics Simulations

2018 ◽  
Vol 19 (11) ◽  
pp. 3321 ◽  
Author(s):  
Evangelos Liamas ◽  
Karina Kubiak-Ossowska ◽  
Richard Black ◽  
Owen Thomas ◽  
Zhenyu Zhang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Electrostatic Interactions ◽  
Charged Surface ◽  
Cell Binding ◽  
Binding Region ◽  
Charged Surfaces ◽  
Fibronectin Fragment ◽  
Dynamics Simulations ◽  
Positively Charged

The effect of surface chemistry on the adsorption characteristics of a fibronectin fragment (FNIII8–10) was investigated using fully atomistic molecular dynamics simulations. Model surfaces were constructed to replicate self-assembled monolayers terminated with methyl, hydroxyl, amine, and carboxyl moieties. It was found that adsorption of FNIII8–10 on charged surfaces is rapid, specific, and driven by electrostatic interactions, and that the anchoring residues are either polar uncharged or of opposing charge to that of the targeted surfaces. On charged surfaces the presence of a strongly bound layer of water molecules and ions hinders FNIII8–10 adsorption. In contrast, adsorption kinetics on uncharged surfaces are slow and non-specific, as they are driven by van der Waals interactions, and the anchoring residues are polar uncharged. Due to existence of a positively charged area around its cell-binding region, FNIII8–10 is available for subsequent cell binding when adsorbed on a positively charged surface, but not when adsorbed on a negatively charged surface. On uncharged surfaces, the availability of the fibronectin fragment’s cell-binding region is not clearly distinguished because adsorption is much less specific.

Estimation of the free energy of adsorption of a polypeptide on amorphous SiO2 from molecular dynamics simulations and force spectroscopy experiments

Soft Matter ◽  
2015 ◽  
Vol 11 (31) ◽  
pp. 6254-6265 ◽  
Author(s):  
Robert Horst Meißner ◽  
Gang Wei ◽  
Lucio Colombi Ciacchi
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Silica Surface ◽  
Force Spectroscopy ◽  
Free Energy Of Adsorption ◽  
Amorphous Sio2 ◽  
Dynamics Simulations ◽  
Smd Simulations

Combination of AFM-force spectroscopy and SMD simulations to assess the free energy of adsorption of a (poly)tetrapeptide on a silica surface.

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