Molecular dynamics study on micelle-small molecule interactions: developing a strategy for an extensive comparison

Molecular dynamics study on micelle-small molecule interactions : developing a strategy for an extensive comparison

Bergström, Christel A. S., 1973- (author): Uppsala universitet,Institutionen för farmaci,Uppsala Univ, Swedish Drug Delivery Ctr, Uppsala, Sweden.

Larsson, Per (author): Uppsala universitet,Institutionen för farmaci,Uppsala Univ, Swedish Drug Delivery Ctr, Uppsala, Sweden.

(creator_code:org_t)

Springer Nature, 2024
2024
English.
In: Journal of Computer-Aided Molecular Design. - : Springer Nature. - 0920-654X .- 1573-4951. ; 38:1

Related links:: https://doi.org/10.1...; show more...; https://uu.diva-port... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

Theoretical predictions of the solubilizing capacity of micelles and vesicles present in intestinal fluid are important for the development of new delivery techniques and bioavailability improvement. A balance between accuracy and computational cost is a key factor for an extensive study of numerous compounds in diverse environments. In this study, we aimed to determine an optimal molecular dynamics (MD) protocol to evaluate small-molecule interactions with micelles composed of bile salts and phospholipids. MD simulations were used to produce free energy profiles for three drug molecules (danazol, probucol, and prednisolone) and one surfactant molecule (sodium caprate) as a function of the distance from the colloid center of mass. To address the challenges associated with such tasks, we compared different simulation setups, including freely assembled colloids versus pre-organized spherical micelles, full free energy profiles versus only a few points of interest, and a coarse-grained model versus an all-atom model. Our findings demonstrate that combining these techniques is advantageous for achieving optimal performance and accuracy when evaluating the solubilization capacity of micelles.Graphical abstractAll-atom (AA) and coarse-grained (CG) umbrella sampling (US) simulations and point-wise free energy (FE) calculations were compared to their efficiency to computationally analyze the solubilization of active pharmaceutical ingredients in intestinal fluid colloids.

NATURVETENSKAP -- Kemi -- Fysikalisk kemi (hsv//swe)
NATURAL SCIENCES -- Chemical Sciences -- Physical Chemistry (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
NATURVETENSKAP -- Kemi -- Teoretisk kemi (hsv//swe)
NATURAL SCIENCES -- Chemical Sciences -- Theoretical Chemistry (hsv//eng)

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Chemical Science ...; and Physical Chemist ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

NATURAL SCIENCES: NATURAL SCIENCES; and Chemical Science ...; and Theoretical Chem ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.