In this article,an effective technique is developed to efficiently obtain the output responses of parameterized structural dynamic problems.This technique is based on the conception of reduced basis method and the usa...In this article,an effective technique is developed to efficiently obtain the output responses of parameterized structural dynamic problems.This technique is based on the conception of reduced basis method and the usage of linear interpolation principle.The original problem is projected onto the reduced basis space by linear interpolation projection,and subsequently an associated interpolation matrix is generated.To ensure the largest nonsingularity,the interpolation matrix needs to go through a timenode choosing process,which is developed by applying the angle of vector spaces.As a part of this technique,error estimation is recommended for achieving the computational error bound.To ensure the successful performance of this technique,the offline-online computational procedures are conducted in practical engineering.Two numerical examples demonstrate the accuracy and efficiency of the presented method.展开更多
Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs.The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmaco...Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs.The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmacological and clinical significance.With our accumulating knowledge on the three-dimensional structure of drug transporters,their oligomerization status has become a topic of intense study due to the possible functional roles carried out by such kind of post-translational modification(PTM).In-depth studies of oligomeric complexes formed among drug transporters as well as their interactions with other regulatory proteins can help us better understand the regulatory mechanisms of these membrane proteins,provide clues for the development of novel drugs,and improve the therapeutic efficacy.In this review,we describe different oligomerization forms as well as their structural basis of major drug transporters in the ATP-binding cassette and solute carrier superfamilies,summarize our current knowledge on the influence of oligomerization for protein expression level and transport function of these membrane proteins,and discuss the regulatory mechanisms of oligomerization.Finally,we highlight the challenges associated with the current oligomerization studies and propose some thoughts on the pharmaceutical application of this important drug transporter PTM.展开更多
基金supported by the National Natural Science Foundation of China (10802028)the Major State Basic Research Development Program of China (2010CB832705)the National Science Fund for Distinguished Young Scholars (10725208)
文摘In this article,an effective technique is developed to efficiently obtain the output responses of parameterized structural dynamic problems.This technique is based on the conception of reduced basis method and the usage of linear interpolation principle.The original problem is projected onto the reduced basis space by linear interpolation projection,and subsequently an associated interpolation matrix is generated.To ensure the largest nonsingularity,the interpolation matrix needs to go through a timenode choosing process,which is developed by applying the angle of vector spaces.As a part of this technique,error estimation is recommended for achieving the computational error bound.To ensure the successful performance of this technique,the offline-online computational procedures are conducted in practical engineering.Two numerical examples demonstrate the accuracy and efficiency of the presented method.
基金This work was supported by Natural Science Foundation of Guangdong Province(grant number 2022A1515010552,China)National Natural Science Foundation of China(grant number U1832101 and 81373473).
文摘Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs.The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmacological and clinical significance.With our accumulating knowledge on the three-dimensional structure of drug transporters,their oligomerization status has become a topic of intense study due to the possible functional roles carried out by such kind of post-translational modification(PTM).In-depth studies of oligomeric complexes formed among drug transporters as well as their interactions with other regulatory proteins can help us better understand the regulatory mechanisms of these membrane proteins,provide clues for the development of novel drugs,and improve the therapeutic efficacy.In this review,we describe different oligomerization forms as well as their structural basis of major drug transporters in the ATP-binding cassette and solute carrier superfamilies,summarize our current knowledge on the influence of oligomerization for protein expression level and transport function of these membrane proteins,and discuss the regulatory mechanisms of oligomerization.Finally,we highlight the challenges associated with the current oligomerization studies and propose some thoughts on the pharmaceutical application of this important drug transporter PTM.
