% This example file for NIH submissions was originally written % by Bruce Donald (http://www.cs.duke.edu/brd/). % % You may freely use, modify and/or distribute this file. % \documentclass[11pt]{nih} %\documentclass{article} %\documentclass[12pt]{article}% % last revision: \def\mydate{2005-06-09 13:58:03 brd} %%%%%%% Two column control \newif\ifdotwocol \dotwocoltrue % two col %\dotwocolfalse % one col \long\def\twocol#1#2{\ifdotwocol{#1}\else{#2}\fi} %%%%%%% \def\mybeforeequation{\footnotesize} %\def\mybeforeequation{\small} %\def\mybeforeequation{} \def\myafterequation{\renewcommand\baselinestretch{1.1}} %\def\myafterequation{} %%%%%%%%%%%%%%%% %%%%%%%%%%%%%%%% \def\citeusmark{$^{\textstyle \star}$} \def\citeus#1#2{\cite{#1}} \def\crow#1#2{#2} %\usepackage{denselists} %\usepackage{scaledfullpage} \usepackage[dvips]{graphicx} \usepackage{color} \usepackage{boxedminipage} \usepackage{amsfonts} \usepackage{amsmath} \usepackage{url} %\usepackage{times} %\usepackage{nih} % PHS 398 Forms %\usepackage{nihblank} % For printing on Blank PHS 398 Forms %\usepackage{confidential} \def\Paper{grant application} \def\paper{application} \def\refappendix{Sec.} \def\poster{(Poster)} %Note from brd \long\def\todo#1{{\bf{To do:}} #1} %\long\def\todo#1{} \def\ICRA{IEEE International Conference on Robotics and Automation (ICRA)} \long\def\squeezable#1{#1} %\def\a5{$\alpha_{_5}$ \def\a5{5} %\def\mycaptionsize{\normalsize} %\def\mycaptionsize{\small} %\def\mycaptionsize{\small} \def\mycaptionsize{\footnotesize} \def\mycodesize{\footnotesize} \def\myeqnsize{\small} \def\sheading#1{{\bf #1:}\ } \def\sheading#1{\subsubsection{#1}} %\def\sheading#1{\bigskip {\bf #1.}} \def\ssheading#1{\noindent {\bf #1.}\ } \newtheorem{hypothesis}{Hypothesis} \long\def\hyp#1{\begin{hypothesis} #1 \end{hypothesis}} \def\cbk#1{[{\em #1}]} \def\R{\mathbb{R}} \def\midv{\mathop{\,|\,}} \def\Fscr{\mathcal{F}} \def\Gscr{\mathcal{G}} \def\Sscr{\mathcal{S}} \def\set#1{{\{#1\}}} \def\edge{\!\rightarrow\!} \def\dedge{\!\leftrightarrow\!} \newcommand{\EOP}{\nolinebreak[1]~~~\hspace*{\fill} $\Box$\vspace*{\parskip}\vspace*{1ex}} %my way of doing starred references \newcommand{\mybibitem}[1]{\bibitem{#1} \label{mybiblabel:#1}} \newcommand{\BC}{[} \newcommand{\EC}{]} \newcommand{\mycite}[1]{\ref{mybiblabel:#1}\nocite{#1}} \newcommand{\starcite}[1]{\ref{mybiblabel:#1}\citeusmark\nocite{#1}} \def\degree{$^\circ$} \def\R{\mathbb{R}} \def\Fscr{\mathcal{F}} \def\set#1{{\{#1\}}} \def\edge{\!\rightarrow\!} \def\dedge{\!\leftrightarrow\!} \long\def\gobble#1{} \def\Jigsaw{{\sc Jigsaw}} \def\ahelix{\ensuremath{\alpha}-helix} \def\ahelices{\ensuremath{\alpha}-helices} \def\ahelical{$\alpha$-helical} \def\bstrand{\ensuremath{\beta}-strand} \def\bstrands{\ensuremath{\beta}-strands} \def\bsheet{\ensuremath{\beta}-sheet} \def\bsheets{\ensuremath{\beta}-sheets} \def\hone{{\ensuremath{^1}\rm{H}}} \def\htwo{{$^{2}$H}} \def\cthir{{\ensuremath{^{13}}\rm{C}}} \def\nfif{{\ensuremath{^{15}}\rm{N}}} \def\hn{{\rm{H}\ensuremath{^\mathrm{N}}}} \def\hnone{{\textup{H}\ensuremath{^1_\mathrm{N}}}} \def\ca{{\rm{C}\ensuremath{^\alpha}}} \def\catwel{{\ensuremath{^{12}}\rm{C}\ensuremath{^\alpha}}} \def\ha{{\rm{H}\ensuremath{^\alpha}}} \def\cb{{\rm{C}\ensuremath{^\beta}}} \def\hb{{\rm{H}\ensuremath{^\beta}}} \def\hg{{\rm{H}\ensuremath{^\gamma}}} \def\dnn{{\ensuremath{d_{\mathrm{NN}}}}} \def\dan{{\ensuremath{d_{\alpha \mathrm{N}}}}} \def\jconst{{\ensuremath{^{3}\mathrm{J}_{\mathrm{H}^{\mathrm{N}}\mathrm{H}^{\alpha}}}} } \def\cbfb{{CBF-$\beta$}} \newtheorem{defn}{Definition} \newtheorem{claim}{Claim} \gobble{ \psfrag{CO}[][]{\colorbox{white}{C}} \psfrag{OO}[][]{\colorbox{white}{O}} \psfrag{CA}[][]{\colorbox{white}{\ca}} \psfrag{HA}[][]{\colorbox{white}{\ha}} \psfrag{CB}[][]{\colorbox{white}{\cb}} \psfrag{HB}[][]{\colorbox{white}{\hb}} \psfrag{HN}[][]{\colorbox{white}{\hn}} \psfrag{N15}[][]{\colorbox{white}{\nfif}} \psfrag{dnn}[][]{\dnn} \psfrag{dan}[][]{\dan} \psfrag{phi}[][]{$\phi$} } \newenvironment{closeenumerate}{\begin{list}{\arabic{enumi}.}{\topsep=0in\itemsep=0in\parsep=0in\usecounter{enumi}}}{\end{list}} \def\CR{\hspace{0pt}} % ``invisible'' space for line break \newif\ifdbspacing %\dbspacingtrue % For double spacing \dbspacingfalse % For normal spacing \ifdbspacing \doublespacing \newcommand{\capspacing}{\doublespace\mycaptionsize} \else \newcommand{\capspacing}{\mycaptionsize} \fi \def\rulefigure{\smallskip\hrule} % \def\codesize{\normalsize} \def\codesize{\small} % Can use macros \be, \ee, \en as shortcuts % for \begin{enumerate}, \end{enumerate}, \item % respectively. \def\be{\begin{enumerate}} % Begin Enumerate \def\ee{\end{enumerate}} % End Enumerate \def\en{\item} % ENtry (item) \def\bi{\begin{itemize}} % Begin Itemize \def\ei{\end{itemize}} % End Itemize \def\bv{\begin{verbatim}} % Begin Verbatim \def\ev{\end{verbatim}} % End Verbatim \def\matlab{{\sc matlab} } \def\amber{{\sc amber} } \def\KS{{$K^*$}} \def\KSM{{K^*}} % K-Star Math \def\KSTM{{\tilde{K}^*}} % K-Star Tilde Math (appx K*) \def\KOP{{$K^{\dagger}_{o}$}} % K-Star Optimal partial \def\KOPM{{K^{\dagger}_{o}}} % K-Star Optimal partial Math \def\KP{{$K^{\dagger}$}} % K-Star partial \def\KPM{{K^{\dagger}}} % K-Star partial Math \def\KTPM{{\tilde{K}^{\dagger}}} % K-Star Tilde partial Math \def\KD{{$K_{_D}$}} \def\KA{{$K_{_A}$}} \def\qpM{{q_{_P}}} \def\qlM{{q_{_L}}} \def\qplM{{q_{_{PL}}}} \def\qSplM{{q^*_{_{PL}}}} \def\KSO{{$K^*_{o}$}} % K-Star Optimal \def\KSOM{{K^*_{o}}} % K-Star Optimal Math \def\CBFB{{CBF-$\beta$}} % Core binding factor beta \def\argmin{\mathop{\mathrm{argmin}}} \def\rhl#1{{\em \underline{RYAN}: *\{{#1}\}*}} \def\set#1{{\left\{ #1 \right\}}} \def\Escr{{\mathcal{E}}} \def\Jscr{{\mathcal{J}}} \def\Kscr{{\mathcal{K}}} \def\th{{$^{{\mathrm{th}}}$}} \newtheorem{proposition}{Proposition} \newtheorem{lemma}{Lemma} \begin{document} \bigskip \appendix %\mydate \setcounter{page}{20} % or whatever %\noindent{\Large\bf Research Plan} \section{Specific Aims} \noindent Realization of novel molecular function requires the ability to alter molecular complex formation. Enzymatic function can be altered by changing enzyme-substrate interactions via modification of an enzyme's active site. A redesigned enzyme may either perform a novel reaction on its native substrates or its native reaction on novel substrates. We propose a novel algorithm for protein redesign, which searches over possible active site mutations and combines a statistical mechanics-derived ensemble-based approach to computing the binding constant with the speed and completeness of a branch-and-bound pruning algorithm. We will develop an efficient$\ldots$ \end{document}