Gene/Protein Disease Symptom Drug Enzyme Compound
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Electrostatic interactions play a pivotal role in the structure and mechanism of action of most biomolecules. There are several conceptually different methods to deal with electrostatics in molecular dynamics simulations. Ionic strength effects are usually introduced using such methodologies and can have a significant impact on the quality of the final conformation space obtained. We have previously shown that full system neutralization can lead to wrong lipidic phases in the 25% PA/PC bilayer (J. Chem. Theory Comput. 2014,10, 5483-5492). In this work, we investigate how two limit approaches to the ionic strength treatment (implicitly with GRF or using full system neutralization with either GRF or PME) can influence the conformational space of the second-generation PAMAM dendrimer. Constant-pH MD simulations were used to map PAMAM's conformational space at its full pH range (from 2.5 to 12.5). Our simulations clearly captured the coupling between protonation and conformation in PAMAM. Interestingly, the dendrimer conformational distribution was almost independent of the ionic strength treatment methods, which is in contrast to what we have observed in charged lipid bilayers. Overall, our results confirm that both GRF with implicit ionic strength and a fully neutralized system with PME are valid approaches to model charged globular systems, using the GROMOS 54A7 force field.
ACS Omega 2018 Feb 28
PMID:Role of Counterions in Constant-pH Molecular Dynamics Simulations of PAMAM Dendrimers. 3002 21

A customizable fluorescent probe platform that can be used to detect various bioactive analytes offers significant potential for engineering a wide range of bioprobes with diverse sensing and imaging functions. Here, we show a facile and innovative strategy for introducing cis-amino-proline as a carrier scaffold, which is appended with three specific functional groups: a target group, a water-soluble group, and fluorophores with triggers. The potency of the designed strategy could be customized to generate variable multifunctional fluorescent probes for detecting bioactive species of interest, including reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), ROS/RSS, and even enzymes. We designed and synthesized five representative water-soluble and organelle-targeted compounds, PMB, PMN, PMD, PRB, and PME, with emission wavelengths of these fluorescent probes varying from blue to red (465, 480, 535, 550, 565, and 640 nm). This strategy could be exemplified by its application to develop a mitochondria-/lysosome-targeting multifunctional fluorescent probe capable of imaging bioactive species of interest in live cells and nude mice.
ACS Sens 2020 07 24
PMID:Establishment of a Customizable Fluorescent Probe Platform for the Organelle-Targeted Bioactive Species Detection. 3262 37